Fat burning during exercise varies widely between individuals

The best heart rate for burning fat differs for each individual and often does not align with the "fat burning zone" on commercial exercise machines, Icahn School of Medicine at Mount Sinai researchers report.

Instead, the researchers said, clinical exercise testing -- a diagnostic procedure to measure a person's physiological response to exercise -- may be a more useful tool to help individuals achieve intended fat loss goals. The study, which used a machine learning-based modeling approach, was published online today in Nutrition, Metabolism and Cardiovascular Disease.

"People with a goal of weight or fat loss may be interested in exercising at the intensity which allows for the maximal rate of fat burning. Most commercial exercise machines offer a 'fat-burning zone' option, depending upon age, sex, and heart rate," says lead author Hannah Kittrell, MS, RD, CDN, a PhD candidate at Icahn Mount Sinai in the Augmented Intelligence in Medicine and Science laboratory. "However, the typically recommended fat-burning zone has not been validated, thus individuals may be exercising at intensities that are not aligned with their personalized weight loss goals."

Ms. Kittrell is also Director of the Mount Sinai Physiolab, a clinical body composition and exercise physiology laboratory at Mount Sinai Morningside.

The term FATmax is sometimes used to represent the exercise intensity and associated heart rate at which the body reaches its highest fat-burning rate during aerobic exercise. At this point, fat is a significant fuel source and therefore this intensity may be of interest to those seeking to optimize fat loss during workouts.

As part of the study, the researchers compared heart rate at FATmax, as measured during a clinical exercise test, to predicted heart rate at percentages of maximal effort within the typically recommended "fat-burning zone." In a sample of 26 individuals, the researchers found that there was poor agreement between measured and predicted heart rate, with a mean difference of 23 beats per minute between the two measures. This suggests that general recommendations for a "fat-burning zone" may not provide accurate guidance.

Next, the researchers plan to study whether individuals who receive a more personalized exercise prescription demonstrate more weight and fat loss, as well as improvement of metabolic health markers that identify health risks like type 2 diabetes, obesity, and heart disease.

"We hope that this work will inspire more individuals and trainers to utilize clinical exercise testing to prescribe personalized exercise routines tailored to fat loss. It also emphasizes the role that data-driven approaches can have toward precision exercise," says senior author Girish Nadkarni, MD, MPH, Irene and Dr. Arthur M. Fishberg Professor of Medicine at Icahn Mount Sinai, Director of The Charles Bronfman Institute of Personalized Medicine, and System Chief, Division of Data-Driven and Digital Medicine, Department of Medicine.

The paper is titled "Discrepancy between predicted and measured exercise intensity for eliciting the maximal rate of lipid oxidation."

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Molecule boosts fat burning

Normally, fat cells store energy. In brown fat cells, however, energy is dissipated as heat -- brown fat thus serves as a biological heater. Most mammals therefore have this mechanism. In humans it keeps newborns warm, in human adults, brown fat activation positively correlates with cardio-metabolic health.

"Nowadays, however, we're toasty warm even in winter," explains Prof. Dr. Alexander Pfeifer from the Institute of Pharmacology and Toxicology at the University of Bonn. "So our body's own furnaces are hardly needed anymore." At the same time, we are eating an increasingly energy-dense diet and are also moving far less than our ancestors. These three factors are poison for brown fat cells: They gradually cease to function and eventually even die. On the other hand, the number of severely overweight people worldwide continues to increase. "Research groups around the world are therefore looking for substances that stimulate brown fat and thus increase fat burning," says Pfeifer.

Dying fat cells boost energy combustion of their neighbors

Together with a group of colleagues, the team at the University of Bonn has now identified a key molecule named inosine that is capable of burning fat. "It is known that dying cells release a mix of messenger molecules that influence the function of their neighbors," explains Dr. Birte Niemann from Pfeifer's research group. Together with her colleague Dr. Saskia Haufs-Brusberg, she planned and conducted the central experiments of the study. "We wanted to know if this mechanism also exists in brown fat."

The researchers therefore studied brown fat cells subjected to severe stress, so that the cells were virtually dying. "We found that they secrete the purine inosine in large quantities," Niemann says. More interesting, however, was how intact brown fat cells responded to the molecular call for help: They were activated by inosine (or simply by dying cells in their vicinity). Inosine thus fanned the furnace inside them. White fat cells also converted to their brown siblings. Mice fed a high-energy diet and treated with inosine at the same time remained leaner compared to control animals and were protected from diabetes.

The inosine transporter seems to play an important role in this context: This protein in the cell membrane transports inosine into the cell, thus lowering the extracellular concentration. Therefore, inosine can no longer exert its combustion-promoting effect.

Drug inhibits the inosine transporter

"There is a drug that was actually developed for coagulation disorders, but also inhibits the inosine transporter," says Pfeifer, who is also a member of the Transdisciplinary Research Areas "Life and Health" and "Sustainable Futures" at the University of Bonn. "We gave this drug to mice, and as a result they burned more energy." Humans also have an inosine transporter. In two to four percent of all people, it is less active due to a genetic variation. "Our colleagues at the University of Leipzig have genetically analyzed 900 individuals," Pfeifer explains. "Those subjects with the less active transporter were significantly leaner on average."

These results suggest that inosine also regulates thermogenesis in human brown fat cells. Substances that interfere with the activity of the transporter could therefore potentially be suitable for the treatment of obesity. The drug already approved for coagulation disorders could serve as a starting point. "However, further studies in humans are needed to clarify the pharmacological potential of this mechanism," Pfeifer says. Neither does he believe that a pill alone will be the solution to the world's rampant obesity pandemic. "But the available therapies are not effective enough at the moment," he stresses. "We therefore desperately need medications to normalize energy balance in obese patients."

The key role played by the body's own heating system is also demonstrated by a major new joined research consortium: The German Research Foundation (DFG) recently approved a Transregional Collaborative Research Center in which the Universities of Bonn, Hamburg and Munich conduct targeted research on brown adipose tissue.

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