The conventional American wisdom about weight loss is simple: a calorie deficit is all that is needed to lose extra pounds, and a moderate consumption of calories in the future is all that is needed to maintain it. For the followers of the idea, the infinite complexity of human biology functions as an important food bank. Anyone who gains a lot of weight or loses weight and increases their performance simply cannot balance the calorie checkbook, which can be corrected by giving up fatty foods or carbohydrates.
Endocrinologists have known for decades that the science of weight is much more complex than calorie deficit and energy expenditure. In 2016, the complexity of the fluctuating peso reached a broad national interest. In a study of former contestants in a season of reality’s weight loss program, The Biggest Loser, scientists discovered that after years, contestants had not only regained much or all of the weight they lost in width, but also Your metabolism is much weaker than most people of size. The bodies of the contestants have struggled for years to regain their weight, in contrast to the efforts and desires of the contestants. No one was sure of the reason.
Together with a team of researchers, Anne-Marie Schmidt, an endocrinologist at the New York University School of Medicine, revealed the mystery. In a new study published today, Schmidt and his team opened a molecular mechanism that controls weight gain and gain in mice: a protein that works to stop animals’ ability to burn fat in times of physical stress, even when they are Dieting or eating too much. This discovery may be the key to understanding why it is so difficult to lose weight for people and even keep it out of reach.
In 1992, Schmidt was studying the complications of diabetes when she and her team did what she called an amazing discovery: humans and other mammals have a protein on the surface of fat cells called receptors for advanced glycan end products, or RAGE, which seem to play previously unnoticed roles in a group from metabolism and inflammatory reactions in the body. Finally, it became clear that the protein was also present in non-glycemic tissues, indicating that RAGE has consequences that go beyond a few chronic diseases.
Schmidt’s recent study found a big difference in weight gain between the two test groups: conventional mice and rabid mice. The last group gained 70 percent less weight than conventional mice, had lower glucose levels and spent more energy while eating the same high-fat diet and doing the same physical activity. Traditional rat bodies hit metabolic brakes, which makes it impossible for them to burn as much energy as their counterparts removed from RAGE.
Schmidt assumes that RAGE may have evolved to protect mammals, including humans, when another meal may not be expected, and the body’s ability to conserve its resources would be a blessing. “However, in a time of abundance, when there is no food shortage, recipients are still present and can continue to play this unfortunate role of storing energy and not allowing it to be spent,” he explained. It makes sense that the body conserves resources when it discovers a potential need, but it feels particularly hard, at least in modern times, that humans can experience the same metabolic slowdown after a delicious meal.
Schmidt’s theories also indicate that the effect of RAGE on chronic infections, which I studied earlier, would have been more beneficial to humans when our lives were much shorter. The answers would have protected short-term health, which would have mattered. “These creatures did not live until an advanced age after reproduction, so they were not required to survive and survive longer,” says Schmidt. The known side effects of RAGE, such as chronic inflammatory diseases, may have no meaning for the well-being of people who have lived to forty years of age.
Although Schmidt warns that translating her findings in mice to human therapies will be a long and delicate process, she is optimistic about the potential. In his new study, he discovered that the weight benefits of RAGE inactivity in new animals could be granted simply by implanting a relatively small amount of brown fatty tissue from mice whose RAGE pathway was eliminated in conventional mice. This announces future treatment for patients with chronic metabolic disorders.
Knowing that the results of the study in mice are not yet known and that their exact translation to humans, Uptal Bajvani, professor and endocrinologist at Columbia University, expressed a similar optimism about the results of the new RAGE. “These data are very important,” he told me in an email, “consistent with the hypothesis that the obesity epidemic is due in part to evolutionary pressure to prevent hunger in stress.” “The current study joins Schmidt’s impressive working group and suggests that methods to reduce RAGE signals in fats can benefit people.”
For thousands of years, mammals may have developed things like RAGE to often overcome their challenging environment. For humans, whose life was greatly extended in the space of only a few generations, this can be a blessing and a curse. To meet the contemporary needs of people whose circumstances have changed at a much faster rate than the ability to evolve to keep up with this, results like Schmidt are leading scientists toward ways to speed up the process.
In order for these developments to have the best chance of improving people’s lives, Schmidt warns against the tendency to overlook human complexity in favor of very simple cultural beliefs, such as the notion that weight loss is simply a deficiency of Calories and willpower. “Losing weight is very difficult,” she says. “Only by studying good things, bad things and how sometimes things that were supposed to be good can go wrong, can we discover the big picture and how to make people’s lives healthier and better.”