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The Biology of Obesity: Why Keeping Weight Off Is So Hard

October 13, 2023

Poster for video Treating Obesity as a Neurometabolic Disease

Losing weight is hard enough to do, but a biological reason explains why maintaining that weight loss can be so challenging.

Obesity is a complex neurometabolic disease, explains Ania Jastreboff, MD, PhD, a Yale Medicine endocrinologist and director of the Yale Obesity Research Center (Y-Weight). When we eat, the body activates nutrient-stimulated hormones, which inform our brains how much fat or energy we are storing. The body then tries to defend an elevated, “defended fat mass set point,” Dr. Jastreboff says.

“Our body has this concerted interest in carrying an appropriate amount of fuel. It doesn't want to carry too little fuel or energy, which it carries as fat, and it doesn’t want to carry too much,” she says. “It wants just the right amount, and we call that sweet spot the ‘defended fat mass set point.’ Our bodies have evolved to carry an appropriate amount of fuel.”

But with people now eating more, exercising and sleeping less, and experiencing increased stress, the defended fat mess set point has increased on a population level. “From an evolutionary perspective, this makes sense. We don’t want to starve,” Dr. Jastreboff says.

Today, anti-obesity medications and surgery can help people maintain weight reduction because they target the disease mechanisms. Anti-obesity medications, for example, mimic nutrient-stimulated hormones and can reset the defended fat mass set point.

“We're at a watershed moment for the treatment of obesity, set in motion by these highly

effective new therapies,” Dr. Jastreboff says. “But there is not necessarily one right thing for everybody. We still need to make lifestyle changes, including nutritious diets and physical activity. Those are critical for health and obesity prevention. But once someone develops the neurometabolic disease of obesity, they need treatments targeting those disease mechanisms.”

In the video above, Dr. Jastreboff talks more about the biology of obesity and how medications can help.

Visit the Yale Obesity Research Center (Y-Weight) to learn more about Yale School of Medicine’s ongoing research on anti-obesity drugs and how they can help people with obesity.