A potential hidden factor in the reason why people have so much trouble losing weight

    Abdulaziz Sobh

    The conventional American wisdom about weight loss is simple: a calorie deficit is all that is required to lose excess weight, and moderate consumption of calories in the future is all that is needed to maintain it. For the supporters of the idea, the infinite complexity of human biology acts as a great nutritional piggy bank. Anyone who gains too much weight or loses weight and recovers it has simply not been able to balance the caloric checkbook, which can be corrected with fatty foods or carbohydrates.

    Endocrinologists have known for decades that the science of weight is much more complicated than calorie deficits and energy expenditures. And in 2016, the voluble complexity of the peso attracted national attention. In a study of former participants in a season of the weight-loss reality show The Biggest Loser, the scientists discovered that years later, participants had not only regained much of the weight they had lost in the program, but also Metabolism. much weaker than most people of their size. The bodies of the contestants had struggled for years to regain the weight, contrary to the efforts and desires of the contestants. No one was sure why.

    Together with a team of researchers, Ann Marie Schmidt, an endocrinologist at the School of Medicine at New York University, has been unraveling the mystery. In a new study published today, Schmidt and his team have unlocked a molecular mechanism that controls weight gain and loss in mice: a protein that reduces the ability of animals to burn fat in times of stress, even when dieting or eat in excess. This discovery could be the key to understanding why it is so difficult for humans to lose weight, and even harder to maintain it.

    In 1992, Schmidt was studying the complications of diabetes when she and her team did what she calls a surprising discovery: humans and other mammals have a protein on the surface of fat cells called the receptor for glycation end products. advanced, or RAGE, that appeared to perform functions previously not observed in a large number of metabolic and inflammatory responses of the body. Finally, it was clear that the protein was also present in non-diabetic tissues, suggesting that RAGE had consequences that went far beyond a few chronic diseases.

    The latest study by Schmidt found a huge difference in weight gain between two test groups: conventional mice and mice whose RAGE pathway had been removed. 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 amount of physical activity. The bodies of conventional mice hit the brakes of metabolism, which prevents them from burning as much energy as their counterparts eliminated with RAGE.

    Schmidt postulates that RAGE could have evolved to protect mammals, including humans, when another food might not be predictably forthcoming and the body's ability to retain its resources would be a blessing. "However, in times of abundance, when there is no shortage of nutrients, the recipient is still present and can continue to play the unfortunate role of hoarding energy and not allowing it to be spent," he explains. It makes sense for the body to conserve resources when it detects a potential need, but it feels particularly cruel, at least in modern times, when humans can experience the same metabolic deceleration after a hearty meal.

    Schmidt also theorizes that the influence of RAGE on chronic inflammation, which she had studied previously, would have been more useful for humans when our life was much shorter. The answers would have protected short-term health, which would have been all that mattered. "These organisms did not live until high ages after reproduction, so it was not necessary to survive and stay alive longer," says Schmidt. The known side effects of RAGE, such as chronic inflammatory diseases, may have been insignificant for the well-being of humans who only lived to be 40 years old.

    Although Schmidt cautions that the translation of her findings in mice to human therapies will be a long and careful process, she is optimistic about the potential. In his new study, he discovered that the weight benefits of RAGE inactivity could be conferred on new animals by simply transplanting a relatively small amount of brown-fat tissue from mice that had been stripped of the RAGE pathway in conventional mice. This is promising for future treatments for patients with metabolic and chronic inflammatory disorders.

    With the qualification that the study findings are in mice and its exact translation to humans is not yet known, Utpal Pajvani, a professor and endocrinologist at Columbia University, expressed similar optimism about the new RAGE findings. "These data are quite interesting and are consistent with the hypothesis that the obesity epidemic is due in part to the evolutionary pressures to prevent hunger in stress," he told me via email. "The current study adds to the impressive work of [Schmidt], and suggests that methods to reduce RAGE signaling in fat may be beneficial for people."

    Over the course of millennia, mammals could have developed things like RAGE to deal with their often challenging environment. For humans, whose lives have been significantly prolonged in the space of only a few generations, that could be both a blessing and a curse. To meet the contemporary needs of people whose circumstances have changed at much faster speeds than the ability of evolution to keep up, findings like Schmidt's are leading scientists to look for ways to accelerate the process.

    For these advances to have the best chance to improve people's lives, Schmidt warns against the tendency to ignore human complexity in favor of too simple cultural beliefs, such as the idea that weight loss is just a shortage of calories and strength. of will. "Weight loss is very, very difficult," she says. "Only by studying the good things, the bad things and how sometimes the things that were supposed to be good to be good can go wrong, we can discover the big picture and how to make people's lives safer and better".


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