Slimming down a colossal fossil whale

A 30 million year-old fossil whale may not be the heaviest animal of all time after all, according to a new analysis by paleontologists at UC Davis and the Smithsonian Institution. The new analysis puts Perucetus colossus back in the same weight range as modern whales and smaller than the largest blue whales ever recorded. The work is published Feb. 29 in PeerJ.

A fossil skeleton of Perucetus was discovered in Peru and described in a paper in Nature last year.

The animal lived about 39 million years ago and belonged to an extinct group of early whales called the basilosaurids.

Perucetus' bones are unusually dense. Mammal bones usually have a solid exterior and are spongy or hollow in the center.

Some animals have more of the center filled in with solid bone, making them dense and heavy.

In aquatic animals, heavy bones can offset buoyancy from body fat and blubber, allowing the animal to maintain neutral buoyancy in water or -- in the case of the hippopotamus -- to walk on river beds.

The fossil whale bones have both extensive in-filling and extra growth of bone on the outside as well, a condition called pachyostosis also seen in some modern aquatic mammals, such as manatees.

Based on a series of assumptions, the original authors (Giovanni Bianucci at the University of Pisa, Italy and colleagues) estimated a body mass for Perucetus of 180 metric tons (ranging from 85 to 340 metric tons). This would make Perucetus as heavy as, or heavier than the biggest blue whales known, even though it is considerably shorter at 17 meters long compared to a blue whale at about 30 meters.

How to weigh a whale?

Professor Ryosuke Motani, a paleobiologist at the UC Davis Department of Earth and Planetary Sciences, said that these estimates would make Perucetus impossibly dense.

"It would have been a job for the whale to stay at the surface, or even to leave the sea bottom -- it would have required continuous swimming against the gravity to do anything in the water," Motani said.

Motani and Nick Pyenson at the Smithsonian Institute National Museum of Natural History reexamined the assumptions used to make those estimates.

The first problem is that Bianucci et al used the fossil bones to estimate the weight of the skeleton, then extrapolated to the weight of the entire animal, assuming that the skeletal and non-skeletal mass would scale at the same rate with increasing body size.

But measurements of other animals show this is not the case, Motani and Pyenson argue.

The original estimates also overestimated how much overall body mass increases as a result of pachyostosis.

But evidence from manatees shows that their bodies are relatively light relative to their skeletal mass.

Motani and Pyenson estimate that the 17-meter long Perucetus weighed in at 60 to 70 tons, considerably less than the known weights of blue whales.

A Perucetus that grew to 20 meters could weigh over 110 tons, still well short of the largest blue whales at 270 tons.

"The new weight allows the whale to come to the surface and stay there while breathing and recovering from a dive, like most whales do," Motani said.

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Polar bears unlikely to adapt to longer summers

More time stranded on land means greater risk of starvation for polar bears, a new study indicates.

During three summer weeks, 20 polar bears closely observed by scientists tried different strategies to maintain energy reserves, including resting, scavenging and foraging.

Yet nearly all of them lost weight rapidly: on average around 1 kilogram, or 2.2 pounds, per day.

Some have speculated that polar bears might adapt to the longer ice-free seasons due to climate warming by acting like their grizzly bear relatives and either rest or eat terrestrial food.

The polar bears in this study tried versions of both strategies -- with little success.

"Neither strategy will allow polar bears to exist on land beyond a certain amount of time. Even those bears that were foraging lost body weight at the same rate as those that laid down," said Charles Robbins, director of the Washington State University Bear Center and co-author of the study in the journal Nature Communications.

"Polar bears are not grizzly bears wearing white coats. They're very, very different."

Usually larger than grizzly bears, adult male polar bears can reach 10 feet in length and weigh 1,500 pounds compared to grizzly bears' 8 feet and 800 pounds.

To maintain that great mass, polar bears rely on the energy-rich fat of seals, which they best catch on the ice.

Little has been known about polar bear energy expenditure and behavior when confined to land, so researchers used collars with video cameras and GPS to track polar bears summering in the western Hudson Bay region of Manitoba, Canada.

They wanted to see what the specialized ice-hunters ate and did during the extended time on land when their preferred seal prey was out of reach.

The researchers also weighed the bears before and after the observation period and measured their energy expenditures.

"We found a real diversity of bear behaviors, and as a result, we saw a diverse range of energy expenditures," said lead author Anthony Pagano, research wildlife biologist with the U.S. Geological Survey Polar Bear Research Program and former WSU post-doctoral researcher.

Many of the adult male polar bears simply laid down to conserve energy, burning calories at rates similar to hibernation.

Others, actively searched for food, consuming bird and caribou carcasses as well as berries, kelp and grasses.

In all, the researchers found a five-fold range in energy expenditure from an adult male that rested 98% of the time to the most active who clocked 330 kilometers (205 miles). Some adult females spent as much as 40% of their time foraging.

Yet all that activity didn't pay off.

"The terrestrial foods did give them some energetic benefit, but ultimately, the bears had to spend more energy to access those resources," said Pagano.

Three polar bears went for long swims -- one swimming 175 kilometers (about 110 miles) across the bay.

Two found carcasses in the water, a beluga and a seal, but neither bear could feed on their finds while swimming nor bring them back to land.

Only one bear out of the 20 gained weight after stumbling across a dead marine mammal on land.

The study focused on the southern-most extent of polar bear range in the western Hudson Bay, where climate warming is likely impacting the bears at a faster rate than other Arctic regions.

The polar bear population in the area has already declined by an estimated 30% since 1987.

This study indicates that polar bears across the Arctic are at risk of starvation as the ice-free period continues to grow.

"As polar bears are forced on land earlier, it cuts into the period that they normally acquire the majority of the energy they need to survive," said Pagano.

"With increased land use, the expectation is that we'll likely see increases in starvation, particularly with adolescents and females with cubs."

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Brain's 'appetite control center' different in people who are overweight or living with obesity

Cambridge scientists have shown that the hypothalamus, a key region of the brain involved in controlling appetite, is different in the brains of people who are overweight and people with obesity when compared to people who are a healthy weight.

The researchers say their findings add further evidence to the relevance of brain structure to weight and food consumption.

Current estimations suggest that over 1.9 billion people worldwide are either overweight or obese. In the UK, according to the Office for Health Improvement & Disparities, almost two-thirds of adults are overweight or living with obesity. This increases an individual's risk of developing a number of health problems, including type 2 diabetes, heart disease and stroke, cancer and poorer mental health.

A large number of factors influence how much we eat and the types of food we eat, including our genetics, hormone regulation, and the environment in which we live. What happens in our brains to tell us that we are hungry or full is not entirely clear, though studies have shown that the hypothalamus, a small region of the brain about the size of an almond, plays an important role.

Dr Stephanie Brown from the Department of Psychiatry and Lucy Cavendish College, University of Cambridge, said: "Although we know the hypothalamus is important for determining how much we eat, we actually have very little direct information about this brain region in living humans. That's because it is very small and hard to make out on traditional MRI brain scans."

The majority of evidence for the role of the hypothalamus in appetite regulation comes from animal studies. These show that there are complex interacting pathways within the hypothalamus, with different cell populations acting together to tell us when we are hungry or full.

To get around this, Dr Brown and colleagues used an algorithm developed using machine learning to analyse MRI brain scans taken from 1,351 young adults across a range of BMI scores, looking for differences in the hypothalamus when comparing individuals who are underweight, healthy weight, overweight and living with obesity.

In a study published today in Neuroimage: Clinical, the team found that the overall volume of the hypothalamus was significantly larger in the overweight and obese groups of young adults. In fact, the team found a significant relationship between volume of the hypothalamus and body-mass index (BMI).

These volume differences were most apparent in those sub-regions of the hypothalamus that control appetite through the release of hormones to balance hunger and fullness.

While the precise significance of the finding is unclear -- including whether the structural changes are a cause or a consequence of the changes in body weight -- one possibility is that the change relates to inflammation. Previous animal studies have shown that a high fat diet can cause inflammation of the hypothalamus, which in turn prompts insulin resistance and obesity. In mice, just three days of a fat-rich diet is enough to cause this inflammation. Other studies have shown that this inflammation can raise the threshold at which animals are full -- in other words, they have to eat more food than usual to feel full.

Dr Brown, the study's first author, added: "If what we see in mice is the case in people, then eating a high-fat diet could trigger inflammation of our appetite control centre. Over time, this would change our ability to tell when we've eaten enough and to how our body processes blood sugar, leading us to put on weight."

Inflammation may explain why the hypothalamus is larger in these individuals, the team say. One suggestion is that the body reacts to inflammation by increasing the size of the brain's specialist immune cells, known as glia.

Professor Paul Fletcher, the study's senior author, from the Department of Psychiatry and Clare College, Cambridge, said: "The last two decades have given us important insights about appetite control and how it may be altered in obesity. Metabolic researchers at Cambridge have played a leading role in this.

"Our hope is that by taking this new approach to analysing brain scans in large datasets, we can further extend this work into humans, ultimately relating these subtle structural brain findings to changes in appetite and eating and generating a more comprehensive understanding of obesity."

The team say more research is needed to confirm whether increased volume in the hypothalamus is a result of being overweight or whether people with larger hypothalami are predisposed to eat more in the first place. It is also possible that these two factors interact with each other causing a feedback loop.

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Despite doubts from quantum physicists: Einstein's theory of relativity reaffirmed

One of the most basic assumptions of fundamental physics is that the different properties of mass -- weight, inertia and gravitation -- always remain the same in relation to each other. Without this equivalence, Einstein's theory of relativity would be contradicted and our current physics textbooks would have to be rewritten. Although all measurements to date confirm the equivalence principle, quantum theory postulates that there should be a violation. This inconsistency between Einstein's gravitational theory and modern quantum theory is the reason why ever more precise tests of the equivalence principle are particularly important.

A team from the Center of Applied Space Technology and Microgravity (ZARM) at University of Bremen, in collaboration with the Institute of Geodesy (IfE) at Leibniz University Hannover, has now succeeded in proving with 100 times greater accuracy that passive gravitational mass and active gravitational mass are always equivalent -- regardless of the particular composition of the respective masses.

The research was conducted within the framework of the Cluster of Excellence "QuantumFrontiers." Today, the team published their findings as a highlights article in the scientific journal Physical Review Letters.

Physical context

Inertial mass resists acceleration. For example, it causes you to be pushed backwards into your seat when the car starts. Passive gravitational mass reacts on gravity and results in our weight on Earth. Active gravitational mass refers to the force of gravitation exerted by an object, or more precisely, the size of its gravitational field. The equivalence of these properties is fundamental to general relativity. Therefore, both the equivalence of inertial and passive gravitational mass and the equivalence of passive and active gravitational mass are being tested with increasing precision.

What was the study about?

If we assume that passive and active gravitational mass are not equal -- that their ratio depends on the material -- then objects made of different materials with a different centre of mass would accelerate themselves. Since the Moon consists of an aluminium shell and an iron core, with centres of mass offset against each other, the Moon should accelerate. This hypothetical change in speed could be measured with high precision, via "Lunar Laser Ranging." This involves pointing lasers from Earth at reflectors on the Moon placed there by the Apollo missions and the Soviet Luna programme. Since then, round trip travel times of laser beams are recorded. The research team analysed "Lunar Laser Ranging" data collected over a period of 50 years, from 1970 to 2022, and investigated such mass difference effects. Since no effect was found, this means that the passive and active gravitational masses are equal to approximately 14 decimal places. This estimate is a hundred times more accurate than the best previous study, dating back to 1986.

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One third of normal-weight individuals are obese, according to study based on body fat percentage

Researchers from the School of Public Health at TAU's Faculty of Medicine examined the anthropometric data of about 3,000 Israeli women and men and concluded that body fat percentage is a much more reliable indicator of an individual's overall health and cardiometabolic risk than the BMI index, widely used in clinics today. The researchers suggest that body fat percentage should become the gold standard in this respect and recommend equipping clinics all over Israel with suitable devices.

The study -- the largest of its kind ever conducted in Israel -- was led by Prof. Yftach Gepner and PhD student Yair Lahav, in collaboration with Aviv Kfir. It and was based on data from the Yair Lahav Nutrition Center in Tel Aviv. The paper was published in Frontiers in Nutrition.

Prof. Gepner: "Israel is a leader in childhood obesity and more than 60% of the country's adults are defined as overweight. The prevailing index in this respect is BMI, based on weight and height measures, which is considered a standard indicator of an individual's general health. However, despite the obvious intuitive connection between excess weight and obesity, the actual measure for obesity is the body's fat content, with the maximum normal values set at 25% for males and 35% for females. Higher fat content is defined as obesity and can cause a range of potentially life-threatening cardiometabolic diseases: heart disease, diabetes, fatty liver, kidney dysfunction, and more. The disparity between the two indexes has generated a phenomenon called 'the paradox of obesity with normal weight' -- higher than normal body fat percentage in normal-weight individuals. In this study we examined the prevalence of this phenomenon in Israel's adult population."

The researchers analyzed the anthropometric data of 3,000 Israeli women and men, accumulated over several years: BMI scores; DXA scans (using X-rays to measure body composition, including fat content); and cardiometabolic blood markers. About one third of the participants, 1,000 individuals, were found to be within the normal weight range. Of these, 38.5% of the women and 26.5% of the men were identified as 'obese with normal weight' -- having excess fat content despite their normal weight. Matching body fat percentage with blood markers for each of these individuals, the study found a significant correlation between 'obesity with normal weight' and high levels of sugar, fat, and cholesterol -- major risk factors for a range of cardiometabolic diseases. At the same time, 30% of the men and 10% of the women identified as overweight were found to have a normal body fat percentage.

Prof. Gepner: "Our findings were somewhat alarming, indicating that obesity with normal weight is much more common in Israel than we had assumed. Moreover, these individuals, being within the norm according to the prevailing BMI index, usually pass 'under the radar'. Unlike people who are identified as overweight, they receive no treatment or instructions for changing their nutrition or lifestyle -- which places them at an even greater risk for cardiometabolic diseases."

Based on their findings, the researchers concluded that body fat percentage is a more reliable indicator of an individual's general health than BMI. Consequently, they suggest that body fat percentage should become the prevailing standard of health, and recommend some convenient and accessible tools for this purpose: skinfold measurements that estimate body fat based on the thickness of the fat layer under the skin; and a user-friendly device measuring the body's electrical conductivity, already used in many fitness centers.

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Artificial intelligence discovers secret equation for 'weighing' galaxy clusters

Astrophysicists at the Institute for Advanced Study, the Flatiron Institute and their colleagues have leveraged artificial intelligence to uncover a better way to estimate the mass of colossal clusters of galaxies. The AI discovered that by just adding a simple term to an existing equation, scientists can produce far better mass estimates than they previously had.

The improved estimates will enable scientists to calculate the fundamental properties of the universe more accurately, the astrophysicists reported March 17, 2023, in the Proceedings of the National Academy of Sciences.

"It's such a simple thing; that's the beauty of this," says study co-author Francisco Villaescusa-Navarro, a research scientist at the Flatiron Institute's Center for Computational Astrophysics (CCA) in New York City. "Even though it's so simple, nobody before found this term. People have been working on this for decades, and still they were not able to find this."

The work was led by Digvijay Wadekar of the Institute for Advanced Study in Princeton, New Jersey, along with researchers from the CCA, Princeton University, Cornell University and the Center for Astrophysics | Harvard & Smithsonian.

Understanding the universe requires knowing where and how much stuff there is. Galaxy clusters are the most massive objects in the universe: A single cluster can contain anything from hundreds to thousands of galaxies, along with plasma, hot gas and dark matter. The cluster's gravity holds these components together. Understanding such galaxy clusters is crucial to pinning down the origin and continuing evolution of the universe.

Perhaps the most crucial quantity determining the properties of a galaxy cluster is its total mass. But measuring this quantity is difficult -- galaxies cannot be 'weighed' by placing them on a scale. The problem is further complicated because the dark matter that makes up much of a cluster's mass is invisible. Instead, scientists deduce the mass of a cluster from other observable quantities.

In the early 1970s, Rashid Sunyaev, current distinguished visiting professor at the Institute for Advanced Study's School of Natural Sciences, and his collaborator Yakov B. Zel'dovich developed a new way to estimate galaxy cluster masses. Their method relies on the fact that as gravity squashes matter together, the matter's electrons push back. That electron pressure alters how the electrons interact with particles of light called photons. As photons left over from the Big Bang's afterglow hit the squeezed material, the interaction creates new photons. The properties of those photons depend on how strongly gravity is compressing the material, which in turn depends on the galaxy cluster's heft. By measuring the photons, astrophysicists can estimate the cluster's mass.

However, this 'integrated electron pressure' is not a perfect proxy for mass, because the changes in the photon properties vary depending on the galaxy cluster. Wadekar and his colleagues thought an artificial intelligence tool called 'symbolic regression' might find a better approach. The tool essentially tries out different combinations of mathematical operators -- such as addition and subtraction -- with various variables, to see what equation best matches the data.

Wadekar and his collaborators 'fed' their AI program a state-of-the-art universe simulation containing many galaxy clusters. Next, their program, written by CCA research fellow Miles Cranmer, searched for and identified additional variables that might make the mass estimates more accurate.

AI is useful for identifying new parameter combinations that human analysts might overlook. For example, while it is easy for human analysts to identify two significant parameters in a dataset, AI can better parse through high volumes, often revealing unexpected influencing factors.

"Right now, a lot of the machine-learning community focuses on deep neural networks," Wadekar explained. "These are very powerful, but the drawback is that they are almost like a black box. We cannot understand what goes on in them. In physics, if something is giving good results, we want to know why it is doing so. Symbolic regression is beneficial because it searches a given dataset and generates simple mathematical expressions in the form of simple equations that you can understand. It provides an easily interpretable model."

The researchers' symbolic regression program handed them a new equation, which was able to better predict the mass of the galaxy cluster by adding a single new term to the existing equation. Wadekar and his collaborators then worked backward from this AI-generated equation and found a physical explanation. They realized that gas concentration correlates with the regions of galaxy clusters where mass inferences are less reliable, such as the cores of galaxies where supermassive black holes lurk. Their new equation improved mass inferences by downplaying the importance of those complex cores in the calculations. In a sense, the galaxy cluster is like a spherical doughnut. The new equation extracts the jelly at the center of the doughnut that can introduce larger errors, and instead concentrates on the doughy outskirts for more reliable mass inferences.

The researchers tested the AI-discovered equation on thousands of simulated universes from the CCA's CAMELS suite. They found that the equation reduced the variability in galaxy cluster mass estimates by around 20 to 30 percent for large clusters compared with the currently used equation.

The new equation can provide observational astronomers engaged in upcoming galaxy cluster surveys with better insights into the mass of the objects they observe. "There are quite a few surveys targeting galaxy clusters [that] are planned in the near future," Wadekar noted. "Examples include the Simons Observatory, the Stage 4 CMB experiment and an X-ray survey called eROSITA. The new equations can help us in maximizing the scientific return from these surveys."

Read more at Science Daily

Excess weight, obesity more deadly than previously believed

Excess weight or obesity boosts risk of death by anywhere from 22% to 91% -- significantly more than previously believed -- while the mortality risk of being slightly underweight has likely been overestimated, according to new CU Boulder research.

The findings, published Feb. 9 in the journal Population Studies, counter prevailing wisdom that excess weight boosts mortality risk only in extreme cases.

The statistical analysis of nearly 18,000 people also shines a light on the pitfalls of using body mass index (BMI) to study health outcomes, providing evidence that the go-to metric can potentially bias findings. After accounting for those biases, it estimates that about 1 in 6 U.S. deaths are related to excess weight or obesity.

"Existing studies have likely underestimated the mortality consequences of living in a country where cheap, unhealthy food has grown increasingly accessible, and sedentary lifestyles have become the norm," said author Ryan Masters, associate professor of sociology at CU Boulder.

"This study and others are beginning to expose the true toll of this public health crisis."

Challenging the obesity paradox

While numerous studies show that heart disease, high blood pressure and diabetes (which are often associated with being overweight) elevate mortality risk, very few have shown that groups with higher BMIs have higher mortality rates.

Instead, in what some call the "obesity paradox," most studies show a U-shaped curve: Those in the "overweight" category (BMI 25-30) surprisingly have the lowest mortality risk. Those in the "obese" category (30-35) have little or no increased risk over the so-called "healthy" category (18.5-25). And both the "underweight" (less than 18.5) and extremely obese (35 and higher) are at increased risk of death.

"The conventional wisdom is that elevated BMI generally does not raise mortality risk until you get to very high levels, and that there are actually some survival benefits to being overweight," said Masters, a social demographer who has spent his career studying mortality trends. "I have been suspicious of these claims."

He noted that BMI, which doctors and scientists often use as a health measure, is based on weight and height only and doesn't account for differences in body composition or how long a person has been overweight.

"It's a reflection of stature at a point in time. That's it," said Masters, noting that Tom Cruise (at 5 feet 7 inches and an extremely muscular 201 pounds at one point), had a BMI of 31.5, famously putting him in the category of "obese." "It isn't fully capturing all of the nuances and different sizes and shapes the body comes in."

To see what happened when those nuances were considered, Masters mined the National Health and Nutrition Examination Survey (NHANES) from 1988 to 2015, looking at data from 17,784 people, including 4,468 deaths.

He discovered that a full 20% of the sample characterized as "healthy" weight had been in the overweight or obese category in the decade prior. When set apart, this group had a substantially worse health profile than those in the category whose weight had been stable.

Masters pointed out that a lifetime carrying excess weight can lead to illnesses that, paradoxically, lead to rapid weight loss. If BMI data is captured during this time, it can skew study results.

"I would argue that we have been artificially inflating the mortality risk in the low-BMI category by including those who had been high BMI and had just lost weight recently," he said.

Meanwhile, 37% of those characterized as overweight and 60% of those with obese BMI had been at lower BMIs in the decade prior. Notably, those who had only recently gained weight had better health profiles.

"The health and mortality consequences of high BMI are not like a light switch," said Masters. "There's an expanding body of work suggesting that the consequences are duration-dependent."

By including people who had spent most of their life at low-BMI weight in the high-BMI categories, previous studies have inadvertently made high BMI look less risky than it is, he said.

When he looked at differences in fat distribution within BMI categories, he also found that variations made a huge difference in reported health outcomes.

Exposing a public health problem

Collectively, the findings confirm that studies have been "significantly affected" by BMI-related bias.

When re-crunching the numbers without these biases, he found not a U-shape but a straight upward line, with those with low BMI (18.5-22.5) having the lowest mortality risk.

Contrary to previous research, the study found no significant mortality risk increases for the "underweight" category.

While previous research estimated 2 to 3% of U.S. adult deaths were due to high BMI, his study pegs the toll at eight times that.

Masters said he hopes the research will alert scientists to be "extremely cautious" when making conclusions based on BMI. But he also hopes the work will draw attention to what he sees not as a problem for individuals alone to solve but rather a public health crisis fueled by an unhealthy or "obesogenic" environment in the U.S.

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Vitamin D benefits and metabolism may depend on body weight

Researchers from Brigham and Women's Hospital, a founding member of the Mass General Brigham healthcare system, have found new evidence that vitamin D may be metabolized differently in people with an elevated body mass index (BMI). The study, appearing in JAMA Network Open, is a new analysis of data from the VITAL trial, a large nationwide clinical trial led by Brigham researchers that investigated whether taking vitamin D or marine omega-3 supplements could reduce the risk of developing cancer, heart disease, or stroke.

"The analysis of the original VITAL data found that vitamin D supplementation correlated with positive effects on several health outcomes, but only among people with a BMI under 25," said first author Deirdre K. Tobias, ScD, an associate epidemiologist in Brigham's Division of Preventive Medicine. "There seems to be something different happening with vitamin D metabolism at higher body weights, and this study may help explain diminished outcomes of supplementation for individuals with an elevated BMI."

Vitamin D is an essential nutrient involved in many biological processes, most notably helping our body absorb minerals, such as calcium and magnesium. While some of the vitamin D we need is made in the body from sunlight, vitamin D deficiencies are often treated with supplementation. Evidence from laboratory studies, epidemiologic research and clinical research has also suggested that vitamin D may play a role in the incidence and progression of cancer and cardiovascular disease, and it was this evidence that prompted the original VITAL trial.

The VITAL trial was a randomized, double-blind, placebo-controlled trial in 25,871 U.S. participants, which included men over the age of 50 and women over the age of 55. All participants were free of cancer and cardiovascular disease at the time of enrollment. While the trial found little benefit of vitamin D supplementation for preventing cancer, heart attack, or stroke in the overall cohort, there was a statistical correlation between BMI and cancer incidence, cancer mortality, and autoimmune disease incidence. Other studies suggest similar results for type 2 diabetes.

The new study aimed to investigate this correlation. The researchers analyzed data from 16,515 participants from the original trial who provided blood samples at baseline (before randomization to vitamin D), as well as 2,742 with a follow-up blood sample taken after two years. The researchers measured the levels of total and free vitamin D, as well as many other novel biomarkers for vitamin D, such as its metabolites, calcium, and parathyroid hormone, which helps the body utilize vitamin D.

"Most studies like this focus on the total vitamin D blood level," said senior author JoAnn E. Manson, MD, DrPH, chief of the Division of Preventive Medicine at the Brigham and principal investigator of VITAL. "The fact that we were able to look at this expanded profile of vitamin D metabolites and novel biomarkers gave us unique insights into vitamin D availability and activity, and whether vitamin D metabolism might be disrupted in some people but not in others."

The researchers found that vitamin D supplementation increased most of the biomarkers associated with vitamin D metabolism in people, regardless of their weight. However, these increases were significantly smaller in people with elevated BMIs.

"We observed striking differences after two years, indicating a blunted response to vitamin D supplementation with higher BMI," Tobias said. "This may have implications clinically and potentially explain some of the observed differences in the effectiveness of vitamin D supplementation by obesity status."

"This study sheds light on why we're seeing 30-40 percent reductions in cancer deaths, autoimmune diseases, and other outcomes with vitamin D supplementation among those with lower BMIs but minimal benefit in those with higher BMIs, suggesting it may be possible to achieve benefits across the population with more personalized dosing of vitamin D," said Manson. "These nuances make it clear that there's more to the vitamin D story."

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Why late-night eating leads to weight gain, diabetes

Northwestern Medicine scientists have uncovered the mechanism behind why eating late at night is linked to weight gain and diabetes.

The connection between eating time, sleep and obesity is well-known but poorly understood, with research showing that over-nutrition can disrupt circadian rhythms and change fat tissue.

New Northwestern research has shown for the first time that energy release may be the molecular mechanism through which our internal clocks control energy balance. From this understanding, the scientists also found that daytime is the ideal time in the light environment of the Earth's rotation when it is most optimal to dissipate energy as heat. These findings have broad implications from dieting to sleep loss and the way we feed patients who require long-term nutritional assistance.

The paper, "Time-restricted feeding mitigates obesity through adipocyte thermogenesis," will be published online today, and in print tomorrow (Oct. 21) in the journal Science.

"It is well known, albeit poorly understood, that insults to the body clock are going to be insults to metabolism," said corresponding study author Dr. Joseph T. Bass, the Charles F. Kettering Professor of Medicine at Northwestern University Feinberg School of Medicine. He also is a Northwestern Medicine endocrinologist.

"When animals consume Western style cafeteria diets -- high fat, high carb -- the clock gets scrambled," Bass said. "The clock is sensitive to the time people eat, especially in fat tissue, and that sensitivity is thrown off by high-fat diets. We still don't understand why that is, but what we do know is that as animals become obese, they start to eat more when they should be asleep. This research shows why that matters."

Bass is also director of the Center for Diabetes and Metabolism and the chief of endocrinology in the department of medicine at Feinberg. Chelsea Hepler, a postdoctoral fellow in the Bass Lab, was the first author and did many of the biochemistry and genetics experiments that grounded the team's hypothesis. Rana Gupta, now at Duke University, was also a key collaborator.

Scrambling the internal clock

In the study, mice, who are nocturnal, were fed a high-fat diet either exclusively during their inactive (light) period or during their active (dark) period. Within a week, mice fed during light hours gained more weight compared to those fed in the dark. The team also set the temperature to 30 degrees, where mice expend the least energy, to mitigate the effects of temperature on their findings.

"We thought maybe there's a component of energy balance where mice are expending more energy eating at specific times," Hepler said. "That's why they can eat the same amount of food at different times of the day and be healthier when they eat during active periods versus when they should be sleeping."

The increase in energy expenditure led the team to look into metabolism of fat tissue to see if the same effect occurred within the endocrine organ. They found that it did, and mice with genetically enhanced thermogenesis -- or heat release through fat cells -- prevented weight gain and improved health.

Hepler also identified futile creatine cycling, in which creatine (a molecule that helps maintain energy) undergoes storage and release of chemical energy, within fat tissues, implying creatine may be the mechanism underlying heat release.

Intermittent fasting and gastric feeding tubes

The science is underpinned by research done by Bass and colleagues at Northwestern more than 20 years ago that found a relationship between the internal molecular clock and body weight, obesity and metabolism in animals.

The challenge for Bass's lab, which focuses on using genetic approaches to study physiology, has been figuring out what it all means, and finding the control mechanisms that produce the relationship. This study brings them a step closer.

The findings could inform chronic care, Bass said, especially in cases where patients have gastric feeding tubes. Patients are commonly fed at night while they sleep, when they're releasing the least amount of energy. Rates of diabetes and obesity tend to be high for these patients, and Bass thinks this could explain why. He also wonders how the research could impact Type II Diabetes treatment. Should meal times be considered when insulin is given, for example?

Hepler will continue to research creatine metabolism. "We need to figure out how, mechanistically, the circadian clock controls creatine metabolism so that we can figure out how to boost it," she said. "Clocks are doing a lot to metabolic health at the level of fat tissue, and we don't know how much yet."

Read more at Science Daily

Prehistoric podiatry: How dinos carried their enormous weight

Scientists have cracked an enduring mystery, discovering how sauropod dinosaurs -- like Brontosaurus and Diplodocus -- supported their gigantic bodies on land.

A University of Queensland and Monash University-led team used 3D modelling and engineering methods to digitally reconstruct and test the function of foot bones of different sauropods.

Dr Andréas Jannel conducted the research during his PhD studies at UQ's Dinosaur Lab and said the team found that the hind feet of sauropod had a soft tissue pad beneath the 'heel', cushioning the foot to absorb their immense weight.

"We've finally confirmed a long-suspected idea and we provide, for the first time, biomechanical evidence that a soft tissue pad -- particularly in their back feet -- would have played a crucial role in reducing locomotor pressures and bone stresses," Dr Jannel said.

"It is mind-blowing to imagine that these giant creatures could have been able to support their own weight on land."

Sauropods were the largest terrestrial animals that roamed the Earth for more than 100 million years.

They were first thought to have been semi-aquatic with water buoyancy supporting their massive weight, a theory disproved by the discovery of sauropod tracks in terrestrial deposits in the mid-twentieth century.

Monash University's Dr Olga Panagiotopoulou said it had also been thought sauropods had feet similar to a modern-day elephant.

"Popular culture -- think Jurassic Park or Walking with Dinosaurs -- often depicts these behemoths with almost-cylindrical, thick, elephant-like feet," Dr Panagiotopoulou said.

"But when it comes to their skeletal structure, elephants are actually 'tip-toed' on all four feet, whereas sauropods have different foot configurations in their front and back feet.

"Sauropod's front feet are more columnar-like, while they present more 'wedge high heels' at the back supported by a large soft tissue pad."

UQ's Associate Professor Steve Salisbury said this was because sauropods and elephants had different evolutionary origins.

"Elephants belong to an ancient order of mammals called proboscideans, which first appeared in Africa roughly 60 million years ago as small, nondescript herbivores, " Associate Professor Salisbury said.

"In contrast, sauropods -- whose ancestors first appeared 230 million years ago -- are more closely related to birds.

"They were agile, two-legged herbivores and it was only later in their evolution that they walked on all fours.

"Crucially, the transition to becoming the largest land animals to walk the earth seems to have involved the adaptation of a heel pad."

The researchers now plan to use the 3D modelling and engineering methods to make further discoveries.

"I'm keen to apply a similar method to an entire limb and to include additional soft tissue such as muscles, which are rarely preserved in fossils," Dr Jannel said.

"We're also excited to study the limbs and feet of other prehistoric animals.

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Highly eccentric black hole merger discovered

For the first time, scientists believe they have detected a merger of two black holes with eccentric orbits. According to a paper published in Nature Astronomy by researchers from Rochester Institute of Technology's Center for Computational Relativity and Gravitation and the University of Florida, this can help explain how some of the black hole mergers detected by LIGO Scientific Collaboration and the Virgo Collaboration are much heavier than previously thought possible.

Eccentric orbits are a sign that black holes could be repeatedly gobbling up others during chance encounters in areas densely populated with black holes such as galactic nuclei. The scientists studied the most massive gravitational wave binary observed to date, GW190521, to determine if the merger had eccentric orbits.

"The estimated masses of the black holes are more than 70 times the size of our sun each, placing them well above the estimated maximum mass predicted currently by stellar evolution theory," said Carlos Lousto, a professor in the School of Mathematical Sciences and a member of the CCRG. "This makes an interesting case to study as a second generation binary black hole system and opens up to new possibilities of formation scenarios of black holes in dense star clusters."

A team of RIT researchers including Lousto, Research Associate James Healy, Jacob Lange '20 Ph.D. (astrophysical sciences and technology), Professor and CCRG Director Manuela Campanelli, Associate Professor Richard O'Shaughnessy, and collaborators from the University of Florida formed to give a fresh look at the data to see if the black holes had highly eccentric orbits before they merged. They found the merger is best explained by a high-eccentricity, precessing model. To achieve this, the team performed hundreds of new full numerical simulations in local and national lab supercomputers, taking nearly a year to complete.

"This represents a major advancement in our understanding of how black holes merge," said Campanelli. "Through our sophisticated supercomputer simulations and the wealth of new data provided by LIGO and Virgo's rapidly advancing detectors, we are making new discoveries about the universe at astonishing rates."

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Forest fires linked to low birth weight in newborns

Women exposed to smoke from landscape fires during pregnancy are more likely to give birth to babies with low or very low birth weights, according to findings published in eLife.

The study is the first to report a link between low birth weight and exposure to fire smoke in low and middle-income countries (LMICs), where 90% of low birth weight infants are born and landscape fires are prevalent.

Landscape fires, such as wildfires, tropical deforestation fires and agricultural biomass burning, play an important role in maintaining terrestrial ecosystems. Yet, landscape fire smoke is triggering a costly and growing global public health problem, causing recurrent episodes of pollution mostly affecting LMICs.

Previous studies have shown that exposure to fire smoke during pregnancy is linked to low birth weight, which itself is a public health problem in LMICs. Reducing the risk of low birth weight is one of the World Health Organization's global targets for 2025.

"Babies with low birth weights are at higher risk of a range of diseases in later life compared to normal weight newborns," explains co-first author Jiajianghui Li, a PhD student at the Institute of Reproductive and Child Health, School of Public Health Science Centre, Peking University, China. "Several studies have shown the effects of landscape fire smoke on acute lung and heart conditions, but the health impacts of these pollutants on susceptible pregnant women are not well known. We wanted to explore the association between birth weight and exposure to fire source pollution across several countries and over a long time period."

The researchers conducted a case-control study in 54 LMICs where they matched 108,137 groups of siblings to their mothers. They used surveys conducted by the US Agency for International Development between 2000 and 2014 to find out information about sibling birth weights and other health and demographic factors. They then assessed exposure to landscape fire pollutants using data on fire emissions from the Global Fire Emission Database and a model that converted this data into ground-surface concentrations of particulate matter in different regions.

Their analysis showed that an increase in exposure of one microgram per cubic metre of fire-sourced particulate matter was associated with a 2.17-gram reduction in birth weight. "The effect was even more pronounced when we looked at whether exposure to fire smoke was linked to low or very low birth weight; for every microgram per cubic metre increase in particulate matter exposure, the risks of low and very low birth weight increased by around three and 12 per cent, respectively," says co-first author Tianjia Guan, an assistant professor at the Department of Health Policy, School of Health Policy and Management, Chinese Academy of Medical Sciences and Peking Union Medical College, China.

The researchers found that very low birth weight was most strongly linked to the pollution. To find out why, they developed a model that looked at the average birth weight of infants within single families. Newborns in families that had lower birth weights on average were more susceptible to the risks of fire smoke pollution than those who had moderate baseline birthweights. "This suggests that other factors affecting maternal and foetal health, such as nutrition or maternal employment status, might make mothers and their developing infants even more susceptible to the risks of pollution," says co-first author Qian Guo, a PhD student at the School of Energy and Environmental Engineering, University of Science and Technology, China.

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Gut microbiota influences the ability to lose weight

Gut microbiota influences the ability to lose weight in humans, according to new research. The findings were published this week in mSystems, an open-access journal of the American Society for Microbiology.

"Your gut microbiome can help or cause resistance to weight loss and this opens up the possibility to try to alter the gut microbiome to impact weight loss," said lead study author Christian Diener, Ph.D., a research scientist at the Institute for Systems Biology in Seattle, Washington.

To conduct their research, Dr. Diener and colleagues focused on a large cohort of individuals who were involved in a lifestyle intervention study. Instead of a specific diet or exercise program, this intervention involved a commercial behavioral coaching program paired with advice from a dietician and nurse coach. The researchers focused on 48 individuals who lost more than 1% of their body weight per month over a 6 to 12 month period and 57 individuals who did not lose any weight and had a stable body mass index (BMI) over the same period. The researchers relied on metagenomics, the study of genetic material recovered from blood and stool samples. The individuals analyzed blood metabolites, blood proteins, clinical labs, dietary questionnaires and gut bacteria in the two groups.

After controlling for age, sex and baseline BMI, the researchers identified 31 baseline stool metagenomic functional features that were associated with weight loss responses. These included complex polysaccharide and protein degradation genes, stress-response genes, respiration-related genes, cell wall synthesis genes and gut bacterial replication rates. A major finding was that the ability of the gut microbiome to break down starches was increased in people who did not lose weight. Another key finding was that genes that help bacteria grow faster, multiply, replicate and assemble cell walls were increased in people who lost more weight.

"Before this study, we knew the composition of bacteria in the gut were different in obese people than in people who were non-obese, but now we have seen that there are a different set of genes that are encoded in the bacteria in our gut that also responds to weight loss interventions," said Dr. Diener. "The gut microbiome is a major player in modulating whether a weight loss intervention will have success or not. The factors that dictate obesity versus nonobesity are not the same factors that dictate whether you will lose weight on a lifestyle intervention."

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Scientists claim that overeating is not the primary cause of obesity

Statistics from the Centers for Disease Control and Prevention (CDC) show that obesity affects more than 40% of American adults, placing them at higher risk for heart disease, stroke, type 2 diabetes, and certain types of cancer. The USDA's Dietary Guidelines for Americans 2020 -- 2025 further tells us that losing weight "requires adults to reduce the number of calories they get from foods and beverages and increase the amount expended through physical activity."

This approach to weight management is based on the century-old energy balance model which states that weight gain is caused by consuming more energy than we expend. In today's world, surrounded by highly palatable, heavily marketed, cheap processed foods, it's easy for people to eat more calories than they need, an imbalance that is further exacerbated by today's sedentary lifestyles. By this thinking, overeating, coupled with insufficient physical activity, is driving the obesity epidemic. On the other hand, despite decades of public health messaging exhorting people to eat less and exercise more, rates of obesity and obesity-related diseases have steadily risen.

The authors of "The Carbohydrate-Insulin Model: A Physiological Perspective on the Obesity Pandemic," a perspective published in The American Journal of Clinical Nutrition, point to fundamental flaws in the energy balance model, arguing that an alternate model, the carbohydrate-insulin model, better explains obesity and weight gain. Moreover, the carbohydrate-insulin model points the way to more effective, long-lasting weight management strategies.

According to lead author Dr. David Ludwig, Endocrinologist at Boston Children's Hospital and Professor at Harvard Medical School, the energy balance model doesn't help us understand the biological causes of weight gain: "During a growth spurt, for instance, adolescents may increase food intake by 1,000 calories a day. But does their overeating cause the growth spurt or does the growth spurt cause the adolescent to get hungry and overeat?"

In contrast to the energy balance model, the carbohydrate-insulin model makes a bold claim: overeating isn't the main cause of obesity. Instead, the carbohydrate-insulin model lays much of the blame for the current obesity epidemic on modern dietary patterns characterized by excessive consumption of foods with a high glycemic load: in particular, processed, rapidly digestible carbohydrates. These foods cause hormonal responses that fundamentally change our metabolism, driving fat storage, weight gain, and obesity.

When we eat highly processed carbohydrates, the body increases insulin secretion and suppresses glucagon secretion. This, in turn, signals fat cells to store more calories, leaving fewer calories available to fuel muscles and other metabolically active tissues. The brain perceives that the body isn't getting enough energy, which, in turn, leads to feelings of hunger. In addition, metabolism may slow down in the body's attempt to conserve fuel. Thus, we tend to remain hungry, even as we continue to gain excess fat.

To understand the obesity epidemic, we need to consider not only how much we're eating, but also how the foods we eat affect our hormones and metabolism. With its assertion that all calories are alike to the body, the energy balance model misses this critical piece of the puzzle.

While the carbohydrate-insulin model is not new -- its origins date to the early 1900s -- The American Journal of Clinical Nutrition perspective is the most comprehensive formulation of this model to date, authored by a team of 17 internationally recognized scientists, clinical researchers, and public health experts. Collectively, they have summarized the growing body of evidence in support of the carbohydrate-insulin model. Moreover, the authors have identified a series of testable hypotheses that distinguish the two models to guide future research.

Adoption of the carbohydrate-insulin model over the energy-balance model has radical implications for weight management and obesity treatment. Rather than urge people to eat less, a strategy which usually doesn't work in the long run, the carbohydrate-insulin model suggests another path that focuses more on what we eat. According to Dr. Ludwig, "reducing consumption of the rapidly digestible carbohydrates that flooded the food supply during the low-fat diet era lessens the underlying drive to store body fat. As a result, people may lose weight with less hunger and struggle."

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Decades after toxic exposure, 9/11 first responders may still lower their risk of lung injury

Losing weight and treating excess levels of fat in the blood may help prevent lung disease in firefighters exposed to dangerous levels of fine particles from fire, smoke, and toxic chemicals on Sept. 11, 2001, a new study shows. Experts have long feared that this exposure would later lead to lung disease in first responders. High body mass index (BMI), an indicator of obesity, and exposure to the highest levels of toxins from the attack on the World Trade Center were the two greatest risk factors for lowered lung function, according to the study authors.

After two decades of research analyzing thousands of first responders, a new investigation led by researchers at NYU Grossman School of Medicine identified a cluster of five factors that predicted lung disease in these patients. Along with excess body fat, the combination of insulin resistance, high blood pressure, and increased levels of sugar and cholesterol in the blood are components of so-called metabolic syndrome, a group of medical issues known to raise the risk of heart disease, stroke, and diabetes.

Adjusting at least one of these factors, the study investigators found, can greatly lower the risk of firefighters' developing lung disease within five years, even 20 years after toxic exposures at Ground Zero. For example, for a male firefighter of average height, a 7-pound weight loss could decrease his risk for lung injury by 20 percent.

"Our findings should reassure World Trade Center first responders that there are steps they can take to protect their lungs even decades after exposure," says study co-lead author Sophia Kwon, DO, MPH. Kwon is a fellow in the Division of Pulmonary, Critical Care, and Sleep at NYU Langone Health.

In work presented earlier this year on 100 overweight 9/11 firefighters, the team found that placing patients on a calorie-restricted Mediterranean diet featuring unrefined grains, olive oil, fruits, and fish reduced their risk of lung disease. Those following the regimen for six months lost nearly 2 BMI points (from an average BMI of about 33 to an average of 31) and had fewer signs of lung disease than they had reported before the study period.

"These results offer firefighters a concrete way to lose weight and achieve the lung-health benefits predicted by our risk model," says study co-lead author George Crowley, BA, a predoctoral fellow at NYU Langone.

Experts had previously understood that first responders who developed metabolic syndrome shortly after 9/11 were more likely to have higher rates of asthma. However, lung injury risks for a firefighter whose metabolic syndrome instead appeared later in life remained unclear until now.

The new study, publishing Sept. 2 in the American Journal of Respiratory and Critical Care Medicine, is part of what is likely the longest-running and most thorough exploration of the impact of metabolic syndrome on lung injury in 9/11 firefighters, according to the study authors. In addition, the investigation is the first to date to quantify how adjusting one or more of these risk factors changes lung disease risk.

For the investigation, the research team analyzed 20 years of data from more than 5,700 firefighters active on 9/11, of whom 1,475 later developed lung disease. Along with BMI, the data collected included smoking history, and whether they had served at the World Trade Center in early morning when pollutant exposure was at its peak.

"The lessons from our investigation can be applied not only to firefighters but to the millions of city dwellers exposed to air pollution on a daily basis," says study senior author and pulmonologist Anna Nolan, MD. "They should be aware that while their environment poses real health risks, they may still minimize their risk of lung disease even if they cannot change their exposure."

Nolan, a professor in the Departments of Medicine and Environmental Health at NYU Langone, cautions that while promising, the Mediterranean diet investigation only examined a small, specific group.

As a result, the research team next plans to expand the study to determine whether the diet could benefit a more diverse population who have been similarly exposed to urban pollutants. They also plan to explore how metabolic syndrome may affect other measures of lung function like asthma, says Nolan.

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Metabolism changes with age, just not when you might think

Most of us remember a time when we could eat anything we wanted and not gain weight. But a new study suggests your metabolism, the rate at which you burn calories, actually peaks much earlier and starts its inevitable decline later than you might think.

The findings appear in the journal Science.

"As we age, there are a lot of physiological changes that occur in the phases of our life such as during puberty and in menopause. . What's odd is that the timing of our 'metabolic life stages' doesn't appear to match the markers we associate with growing up and getting older," said study co-author Jennifer Rood, PhD, Associate Executive Director for Cores and Resources at Pennington Biomedical Research Center.

Four Pennington Biomedical researchers were part of an international team of scientists who analyzed the average calories burned by more than 6,600 people as they went about their daily lives. The participants' ages ranged from one week old to 95 years, and they lived in 29 different countries. The other Pennington Biomedical scientists are Peter Katzmarzyk, PhD, Associate Executive Director for Population and Public Health Sciences; Corby Martin, PhD, Professor and Director, Ingestive Behavior Laboratory; and Eric Ravussin, PhD, Associate Executive Director for Clinical Science.

Most previous large-scale studies measured how much energy the body uses for basic vital functions -- breathing, digesting, and pumping blood -- the calories you need just to stay alive. But basic functions account for just 50 percent to 70 percent of the calories we burn each day. They don't include the energy we spend doing everything else: washing the dishes, walking the dog, breaking a sweat at the gym, even just thinking or fidgeting.

To come up with a number for total daily energy expenditure, the researchers turned to the "doubly labeled water" method. It's a urine test that involves having a person drink water in which the hydrogen and oxygen in the water molecules have been replaced with naturally occurring "heavy" forms, and then measures how quickly they're flushed out.

Scientists have used the technique -- considered the gold standard for measuring daily energy expenditure during normal daily life outside of the lab -- to measure energy expenditure in humans since the 1980s. But previous studies were limited in size and scope due to cost. To get around that limitation, multiple labs shared their data in a single database, to see if they could tease out truths hidden or only hinted at in previous studies.

Pooling and analyzing energy expenditures across the entire lifespan revealed some surprises.

"Some people think of their teens and 20s as the age when their calorie-burning potential hits its peak," Dr. Katzmarzyk said. "But the study shows that, pound for pound, infants had the highest metabolic rates of all."

Energy needs shoot up during the first 12 months of life. By their first birthdays, babies burn calories 50 percent faster for their body size than adults.

And that's not just because infants are busy tripling their birth weight in their first year.

"The babies grow rapidly, which accounts for much of the effect. However, after you control for this, their energy expenditures tend to be higher than what you would expect for their body size," Dr. Martin said.

An infant's explosive metabolism may help explain why children who don't get enough to eat during this developmental stage are less likely to survive and grow up to be healthy adults.

"More research is needed to better understand the metabolism of babies. We need to know what is driving higher energy expenditures," Dr. Martin said.

After the initial surge in infancy, a person's metabolism slows by about 3 percent each year until our 20s, when it levels off into a new normal.

Surprisingly, the growth spurts of adolescence didn't generate an increase in daily calorie needs after researchers took body size into account. Another surprise? People's metabolisms were most stable from their 20s through their 50s. Calorie needs during pregnancy grew no more than expected.

The findings suggest that other factors lie behind the so-called "middle-age spread."

The data suggest that our metabolisms don't really start to decline again until after age 60. The slowdown is gradual, only 0.7 percent a year. But a person in their 90s needs 26 percent fewer calories each day than someone in midlife.

Lost muscle mass as we get older may be partly to blame, the researchers say, since muscle burns more calories than fat. But it's not the whole picture.

"We took dwindling muscle mass into account. After 60, a person's cells slow down," Dr. Ravussin said.

The patterns held even when differing activity levels were taken into account.

Aging goes hand in hand with so many other physiological changes that it has been difficult to parse what drives the shifts in energy expenditure. But the new research supports the idea that it's more than age-related changes in lifestyle or body composition.

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Your stomach may be the secret to fighting obesity

Scientists believe a stomach-specific protein plays a major role in the progression of obesity, according to new research in Scientific Reports. The study co-authored by an Indiana University School of Medicine researcher, could help with development of therapeutics that would help individuals struggling with achieving and maintaining weight loss.

Researchers focused on Gastrokine-1 (GKN1) -- a protein produced exclusively and abundantly in the stomach. Previous research has suggested GKN1 is resistant to digestion, allowing it to pass into the intestine and interact with microbes in the gut.

In the Scientific Reports study, researchers show that inhibiting GKN1 produced significant differences in weight and levels of body fat in comparison to when the protein was expressed.

"While diet and exercise are critical to maintaining a healthy weight, some individuals struggle with weight loss -- even in cases of bariatric surgery, maintaining weight loss can be a challenge," said David Boone, PhD, associate professor of microbiology and immunology at IU School of Medicine, an adjunct professor in the Department of Biology at the University of Notre Dame and a co-author of the study. "These results are an example of how a better understanding of the gut microbiome and the physiological aspects of obesity -- how our bodies regulate metabolism and accumulate body fat -- could help inform new therapies."

Data from the Centers for Disease Control show adult obesity rates have increased to 42.4 percent in the United States. In addition to increasing an individual's risk of stroke, diabetes, certain cancers and other health issues, obesity can also increase the risk of severe illness due to COVID-19.

Boone and his team conducted a microbiome analysis of mouse models with and without the GKN1 protein expressed. Researchers measured food intake, caloric extraction, blood sugar, insulin and triglyceride levels. They used magnetic resonance imagining to monitor body composition. The team also calculated energy expenditure and observed inflammation levels.

Models without GKN1 weighed less and had lower levels of total body fat and higher percentages of lean mass -- despite consuming the same amount of food. When put on a high-fat diet, models without GKN1 showed a resistance to weight gain, increased body fat and hepatic inflammation, which can lead to liver disease. Researchers also found no evidence of adverse effects such as cancer, diabetes, loss of appetite, malabsorption or inflammation -- and results were consistent in male and female models.

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More belly weight increases danger of heart disease even if BMI does not indicate obesity

People with abdominal obesity and excess fat around the body's mid-section and organs have an increased risk of heart disease even if their body mass index (BMI) measurement is within a healthy weight range, according to a new Scientific Statement from the American Heart Association published today in the Association's flagship journal, Circulation.

"This scientific statement provides the most recent research and information on the relationship between obesity and obesity treatment in coronary heart disease, heart failure and arrhythmias," said Tiffany M. Powell-Wiley, M.D., M.P.H., FAHA, chair of the writing committee and a Stadtman Tenure-Track Investigator and chief of the Social Determinants of Obesity and Cardiovascular Risk Laboratory in the Division of Intramural Research at the National Heart, Lung, and Blood Institute at the National Institutes of Health in Bethesda, Maryland. "The timing of this information is important because the obesity epidemic contributes significantly to the global burden of cardiovascular disease and numerous chronic health conditions that also impact heart disease."

A greater understanding of obesity and its impact on cardiovascular health highlights abdominal obesity, sometimes referred to as visceral adipose tissue, or VAT, as a cardiovascular disease risk marker. VAT is commonly determined by waist circumference, the ratio of waist circumference to height (taking body size into account) or waist-to-hip ratio, which has been shown to predict cardiovascular death independent of BMI.

Experts recommend both abdominal measurement and BMI be assessed during regular health care visits because a high waist circumference or low waist-to-hip ratio, even in healthy weight individuals, could mean an increased risk of heart disease. Abdominal obesity is also linked to fat accumulation around the liver that often leads to non-alcoholic fatty liver disease, which adds to cardiovascular disease risk.

"Studies that have examined the relationship between abdominal fat and cardiovascular outcomes confirm that visceral fat is a clear health hazard," said Powell-Wiley.

The risk-inducing power of abdominal obesity is so strong that in people who are overweight or have obesity based on BMI, low levels of fat tissue around their midsection and organs could still indicate lower cardiovascular disease risks. This concept, referred to as "metabolically healthy obesity," seems to differ depending on race/ethnicity and sex.

Worldwide, around 3 billion people are overweight (BMI = 25 to 29.9 kg/m2) or have obesity obese(BMI ?30 kg/m2). Obesity is a complex disease related to many factors, including biologic, psychological, environmental and societal aspects, all of which may contribute to a person's risk for obesity. Obesity is associated with greater risk of coronary artery disease and death due to cardiovascular disease and contributes to many cardiovascular risk factors and other health conditions, including dyslipidemia (high cholesterol), type 2 diabetes, high blood pressure and sleep disorders.

For this statement, experts evaluated research on managing and treating obesity, particularly abdominal obesity. The writing group reports that reducing calories can reduce abdominal fat, and the most beneficial physical activity to reduce abdominal obesity is aerobic exercise. Their analysis found that meeting the current recommendations of 150 min/week of physical activity may be sufficient to reduce abdominal fat, with no additional loss from longer activity times. Exercise or a combination of dietary change and physical activity has been shown in some instances to reduce abdominal obesity even without weight loss.

Lifestyle changes and subsequent weight loss improve blood sugar, blood pressure, triglyceride and cholesterol levels -- a cluster of factors referred to as metabolic syndrome -- and reduce inflammation, improve blood vessel function and treat non-alcoholic fatty liver disease. However, studies of lifestyle change programs have not shown a reduction in coronary artery disease events (such as heart attack or chest pain).

In contrast, bariatric surgery for weight loss treatment is associated with a reduction in coronary artery disease risk compared to non-surgical weight loss. This difference may be attributed to the larger amount of weight loss and the resultant changes in metabolism that are typical after bariatric surgery.

"Additional work is needed to identify effective interventions for patients with obesity that improve cardiovascular disease outcomes and reduce cardiovascular disease mortality, as is seen with bariatric surgery," said Powell-Wiley.

The statement also addresses the "obesity paradox," which is sometimes observed in research, particularly in populations that have overweight or have Class I obesity (BMI = 30 to 34.9 kg/m2). The paradox suggests that even though overweight and obesity are strong risk factors for the development of cardiovascular disease, they are not always a risk factor for negative cardiovascular outcomes. The writing group notes that people with overweight or obesity are often screened earlier for cardiovascular disease than people with healthy weight, thus resulting in earlier diagnoses and treatment.

"The underlying mechanisms for the obesity paradox remain unclear," said Powell-Wiley. "Despite the existence of the paradox for short-term cardiovascular disease outcomes, the data show that patients with overweight or obesity suffer from cardiovascular disease events at an earlier age, live with cardiovascular disease for more of their lives and have a shorter average lifespan than patients with normal weight."

In reviewing the effects of obesity on a common heart rhythm disorder, the writing group reports there is now "convincing data" that obesity may cause atrial fibrillation, a quivering or irregular heartbeat. Estimates suggest obesity may account for one-fifth of all atrial fibrillation cases and 60% of recently documented increases in people with atrial fibrillation. Research has demonstrated people with atrial fibrillation who had intense weight loss experienced a significant reduction in cumulative time spent in atrial fibrillation.

"The research provides strong evidence that weight management be included as an essential aspect of managing atrial fibrillation, in addition to the standard treatments to control heart rate, rhythm and clotting risk," said Powell-Wiley.

The statement identifies areas of future research, including a call for further study of lifestyle interventions that may be most effective in decreasing visceral adiposity and improving cardiovascular outcomes. Powell-Wiley said, "It's important to understand how nutrition can be personalized based on genetics or other markers for cardiovascular disease risk.

Read more at Science Daily

Losing weight through exercise

Worldwide 39 percent of the adults were overweight in 2016, according to statistics of the World Health Organization. In the US the prevalence of obesity was 42.4 percent in 2017/2018, according to a survey of the National Center for Health Statistics (NCHS).

Concurrently millions of people want to lose weight. Physical exercise is an important option to achieve this. After all, more calories are consumed through sport than when sitting, standing or lying down.

But what influence does sport have on (direct) eating habits? Scientists at the Technical University of Munich (TUM) and the University of Nebraska (USA) have now investigated this question for the first time.

Randomized study

"In the sports context, we have the phenomenon of people overeating after physical activity," said Prof. Köhler, Professor of Exercise, Nutrition and Health at the Technical University of Munich. "People want to reward themselves and their bodies for being active. So we use a hypothetical experiment to find out why people eat more after exercise compared to when they don't exercise."

The aim of a randomized crossover study was to investigate the influence of exercise on hypothetical decisions regarding the amount and timing of food intake. For this purpose, 41 healthy participants (23 women, 18 men) aged between 19 and 29 years with an average BMI of 23.7 were randomly assigned to either a 45-minute exercise session or a rest period of equal duration at the first visit and completed the other study condition at the second visit.

Subjective assessment of hunger and satiety

In each case, the training group answered an electronic questionnaire before the physical activity about their subjective assessment of hunger and satiety, preferred amount of food to eat, and choice between foods that differed in timing of consumption. Subjects indicated their food quantity preferences by listing their desired portion size of each food. Preferences were obtained for both immediate and later consumption of the food after four hours.

After answering the first questionnaire, participants performed 45 minutes of aerobic exercise on a bicycle ergometer. Immediately afterwards, they completed the electronic questionnaire a second time and then a third time after a 30-minute break. The procedure for the group without training was identical; instead of 45 minutes of physical activity, these participants had a rest break.

Compared to the rest break, exercise provided a greater increase in the amount of food chosen, both immediately after exercise and 30 minutes afterwards. Physical activity also resulted in a greater increase in preference for immediate food consumption both immediately after exercise and 30 minutes afterwards.

Weight loss through exercise

"Based on this study, we were able to show for the first time that certain characteristics, such as the amount and 'urgency' with which a person wants to eat, change over the course of physical exertion," said Prof. Köhler, classifying the results. "These findings help us develop new interventions to optimize weight loss through exercise."

"The actual results suggest that physical exertion can entice those who do sport to eat larger amounts of food more quickly after the training session," says Prof. Köhler. "Since weight loss is a main motivation for exercising for many, and failure to achieve the desired weight loss makes it likely to quit exercising, it could be a good strategy to think about what you want to eat afterwards before you start to exercise."

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Deciphering the genetics behind eating disorders

 Anorexia nervosa, bulimia nervosa and binge-eating disorder are the three main eating disorders that 4 out of in 10 individuals living in Western Europe will experience at some point in their lives. In recent years, studies on the genetic basis of anorexia nervosa have highlighted the existence of predisposing genetic markers, which are shared with other psychiatric disorders. By analysing the genome of tens of thousands of British people, a team from the University of Geneva (UNIGE), the University Hospitals of Geneva (HUG), King's College London, the University College London, the University of North Carolina (UNC) and The Icahn School of Medicine at Mount Sinai have built on these initial results by discovering similarities between the genetic bases of these various eating disorders, and those of other psychiatric disorders. Eating disorders differ in their genetic association with anthropometric traits, like weight, waist circumference or body mass index. Thus, genetic predisposition to certain weight traits may be a distinctive feature of anorexia nervosa, bulimia nervosa or binge-eating disorder. The study is published in the International Journal of Eating Disorders.

"Previous studies, which highlighted a genetic association between a high risk of anorexia nervosa and a low risk of obesity, have begun to lift the veil on certain aspects of how eating disorders develop that had been mostly neglected until then," explains Nadia Micali, Professor at the Department of Psychiatry at UNIGE Faculty of Medicine and Head of the Division of child and adolescent psychiatry at the HUG, who directed this work. She continues, "However, the same work has not been done for the two other major eating disorders: bulimia nervosa and binge-eating disorder. The goal of our study was to understand similiarities and differences amongst all eating disorders in the role of genes governing body weight."

The genome of more than 20,000 people examined

To understand the similarities and differences between the genetic patterns of anorexia nervosa, bulimia nervosa and binge-eating disorder, the research team analysed the genomes of more than 20,000 people. These were taken from two large population-based studies conducted in the UK: the UK Biobank and the Avon Longitudinal Study of Parents and Children.

First author, Dr Christopher Hübel, from King's College London said: "We were able to access volunteer's DNA, their basic health data (weight, age, etc.) and responses to health questionnaires, including possible psychiatric disorders and their eating disorder history. We are grateful for this access as we were able to conduct multifactorial analyses and calculate more than 250 polygenic scores for each person. Each polygenic score sums the risk genes involved in a specific trait, such as depression, for example. We calculated polygenic scores for psychiatric disorders, such as schizophrenia and obsessive-compulsive disorder, and metabolic and physical traits, including insulin sensitivity, obesity and high BMI." Thus, the higher the score, the greater the genetic risk, whether it is blue eyes or the development of a given disease.

The research team then examined the associations between the polygenic scores of these volunteers (representing genetic liability to psychiatric disorders, metabolic and physical traits) and eating disorders.

A combination of psychiatric and body weight regulation genetic risk

The study shows that while there are great genetic similarities between anorexia nervosa, bulimia nervosa and binge-eating disorder, there are also notable differences.

Nadia Micali details these results: "The similarities lie in the association with psychiatric risks: anorexia nervosa, bulimia nervosa and binge-eating disorder share genetic risk with certain psychiatric disorders, in particular for schizophrenia and depression, thus confirming the strong psychiatric component of these diseases. However, the big difference concerns the associated genetics of body weight regulation, which are opposite between anorexia on the one hand, and bulimia nervosa and binge-eating disorder on the other, the latter being linked to a high genetic risk of obesity, and high BMI."

A genetic predisposition to a heavy weight versus a light weight may constitute a determining factor that pushes individuals with similar psychiatric genetic risk to different eating disorders.

"The metabolic and physical component would therefore direct the individual either towards anorexia nervosa or towards bulimia nervosa or binge-eating disorder," analyses Nadia Micali. "Moreover, this study confirms a clear genetic relationship between binge-eating disorder and attention deficit hyperactivity disorder (ADHD), that was already clinically observed, which might be linked to greater impulsivity, which is shared by these disorders." The role of genetic patterns in body weight regulation identified in this study provides a better understanding of the genetic basis of eating disorders, and of how they differ in their genetic marking despite their similarities. This work could lead to better understand the development of eating disorders.

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