Lab-grown fat could give cultured meat real flavor and texture

Researchers have successfully bulk-produced fat tissue in the lab that has a similar texture and make-up to naturally occurring fats from animals.

The results, described in a study published today in eLife, could be applied to the production of cultured meat grown entirely from cells, giving it a more realistic texture and flavour.

Cultivated meat has been making waves in the news lately, with reports from startup companies around the world developing cell-grown chicken, beef, pork and fish -- mostly in early stages of development, not ready for large-scale production and with a couple of exceptions, not yet approved for commercial sale. Most of those products in development are in the form of an unstructured mixture of cells -- like chicken nuggets rather than a slice of chicken breast. What is lacking is the texture of real meat, created by muscle fibres, connective tissue and fat -- and it's the fat that gives meat flavour.

In fact, consumer testing with natural beef of different fat content showed that the highest scores were registered for beef containing 36% fat.

However, producing cultured fat tissue in sufficient quantities has been a major challenge because, as the fat grows into a mass, the cells in the middle become starved of oxygen and nutrients. In nature, blood vessels and capillaries deliver oxygen and nutrients throughout the tissue. Researchers still have no way to replicate that vascular network at a large scale in lab grown tissue, so they can only grow muscle or fat to a few millimetres in size.

To get around this limitation, the researchers grew fat cells from mice and pigs first in a flat, two-dimensional layer, then harvested those cells and aggregated them into a three-dimensional mass with a binder such as alginate and mTG, which are both already used in some foods.

"Our goal was to develop a relatively simple method of producing bulk fat. Since fat tissue is predominantly cells with few other structural components, we thought that aggregating the cells after growth would be sufficient to reproduce the taste, nutrition and texture profile of natural animal fat," says first author John Yuen Jr, a graduate student at the Tufts University Center for Cellular Architecture (TUCCA), Massachusetts, US. "This can work when creating the tissue solely for food, since there's no requirement to keep the cells alive once we gather the fat in bulk."

The aggregated fat cells immediately had the appearance of fat tissue, but to see if they truly reproduced the features of native fat from animals, the team carried out a series of further experiments.

First, they explored the texture, by compressing the fat tissue and seeing how much pressure it could withstand compared to natural animal fat. They found that cell-grown fat bound with sodium alginate was able to withstand a similar amount of pressure to fat from livestock and poultry, but the cell-grown fat that was bound with mTG behaved more like rendered fat -- similar to lard or tallow. This suggests it could be possible to fine-tune the texture of cultured fat, so it best resembles the real-life texture of fat within meat, using different types and amounts of binders.

Cooking releases hundreds of compounds that add flavour to the meat, and most of those compounds originate from fat, including lipids and their component fatty acids. The team therefore examined the composition of molecules from the cell-grown fat and found that the mix of fatty acids from cultured mouse fat differed from native mouse fat. However, the cultured pig fat had a much closer fatty acid profile to the native tissue. The team's preliminary research suggests it might be possible to supplement growing fat cells with the required lipids to ensure that they more closely match the composition of natural meat.

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Eating late increases hunger, decreases calories burned, and changes fat tissue

Obesity afflicts approximately 42 percent of the U.S. adult population and contributes to the onset of chronic diseases, including diabetes, cancer, and other conditions. While popular healthy diet mantras advise against midnight snacking, few studies have comprehensively investigated the simultaneous effects of late eating on the three main players in body weight regulation and thus obesity risk: regulation of calorie intake, the number of calories you burn, and molecular changes in fat tissue. A new study by investigators from Brigham and Women's Hospital, a founding member of the Mass General Brigham healthcare system, found that when we eat significantly impacts our energy expenditure, appetite, and molecular pathways in adipose tissue. Their results are published in Cell Metabolism.

"We wanted to test the mechanisms that may explain why late eating increases obesity risk," explained senior author Frank A. J. L. Scheer, PhD, Director of the Medical Chronobiology Program in the Brigham's Division of Sleep and Circadian Disorders. "Previous research by us and others had shown that late eating is associated with increased obesity risk, increased body fat, and impaired weight loss success. We wanted to understand why."

"In this study, we asked, 'Does the time that we eat matter when everything else is kept consistent?'" said first author Nina Vujovic, PhD, a researcher in the Medical Chronobiology Program in the Brigham's Division of Sleep and Circadian Disorders. "And we found that eating four hours later makes a significant difference for our hunger levels, the way we burn calories after we eat, and the way we store fat."

Vujovic, Scheer and their team studied 16 patients with a body mass index (BMI) in the overweight or obese range. Each participant completed two laboratory protocols: one with a strictly scheduled early meal schedule, and the other with the exact same meals, each scheduled about four hours later in the day. In the last two to three weeks before starting each of the in-laboratory protocols, participants maintained fixed sleep and wake schedules, and in the final three days before entering the laboratory, they strictly followed identical diets and meal schedules at home. In the lab, participants regularly documented their hunger and appetite, provided frequent small blood samples throughout the day, and had their body temperature and energy expenditure measured. To measure how eating time affected molecular pathways involved in adipogenesis, or how the body stores fat, investigators collected biopsies of adipose tissue from a subset of participants during laboratory testing in both the early and late eating protocols, to enable comparison of gene expression patterns/levels between these two eating conditions.

Results revealed that eating later had profound effects on hunger and appetite-regulating hormones leptin and ghrelin, which influence our drive to eat. Specifically, levels of the hormone leptin, which signals satiety, were decreased across the 24 hours in the late eating condition compared to the early eating conditions. When participants ate later, they also burned calories at a slower rate and exhibited adipose tissue gene expression towards increased adipogenesis and decreased lipolysis, which promote fat growth. Notably, these findings convey converging physiological and molecular mechanisms underlying the correlation between late eating and increased obesity risk.

Vujovic explains that these findings are not only consistent with a large body of research suggesting that eating later may increase one's likelihood of developing obesity, but they shed new light on how this might occur. By using a randomized crossover study, and tightly controlling for behavioral and environmental factors such as physical activity, posture, sleep, and light exposure, investigators were able to detect changes the different control systems involved in energy balance, a marker of how our bodies use the food we consume.

In future studies, Scheer's team aims to recruit more women to increase the generalizability of their findings to a broader population. While this study cohort included only five female participants, the study was set up to control for menstrual phase, reducing confounding but making recruiting women more difficult. Going forward, Scheer and Vujovic are also interested in better understanding the effects of the relationship between meal time and bedtime on energy balance.

"This study shows the impact of late versus early eating. Here, we isolated these effects by controlling for confounding variables like caloric intake, physical activity, sleep, and light exposure, but in real life, many of these factors may themselves be influenced by meal timing," said Scheer. "In larger scale studies, where tight control of all these factors is not feasible, we must at least consider how other behavioral and environmental variables alter these biological pathways underlying obesity risk. "

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