Overeating? Researchers Discover That These Cells May Be To Blame

A new study reveals that a region of the brain called the amygdala may be responsible for overeating. 

The amygdala, a region of the brain, is responsible for strong emotions such as fear. Researchers have recently shown that the amygdala may also be to blame for overeating. Professor Bo Li of Cold Spring Harbor Laboratory (CSHL) has identified a section of neurons in the amygdala that causes mice to eat fatty or sugary foods even when they are not hungry. Therapeutics targeting these neurons might lead to new obesity treatments with few side effects.

Mice, like the majority of humans, like foods that are high in fat and sugar. Instead of eating these foods to survive, they may do so for enjoyment. They may indulge in these treats for pleasure, rather than for survival. The neurons Li and his colleagues studied trigger this behavior, called hedonic eating.

Li notes: “Even if the animal is supposed to stop eating because they are already full, if those neurons are still active, it can still drive those animals to eat more.”

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When the neurons Li studied were inactivated, it protected mice against long-term weight gain. The left image shows lipid droplets (red) in the liver of a mouse that had those neurons turned off. In contrast, the right image shows many more lipid droplets in mice that did not have the neurons turned off. Credit: Bo Li Lab/CSHL/2022

According to Li, almost no one succeeds in long-term weight management while treating obesity. Metabolic processes in the body often undo any progress made. Therapeutics may improve the chances of successful treatment, yet many drugs have undesirable side effects.

“The medications currently available to aid weight management can cause significant side effects. So, a more targeted approach is needed,” Li says. “Identifying the brain circuitry that controls eating is important for developing better treatment options for people who struggle to control their weight.”

When the team switched off the specific neurons, mice weren’t drawn to the fatty, sugary foods that had tempted them before. “They just happily ate and stayed healthy,” Li says. “They not only stopped gaining weight but also seemed to be much healthier overall.” Switching these neurons off reduced overeating and protected against obesity. It also boosted the animals’ physical activity, leading to weight loss and better metabolic health.

Li and his team are exploring ways to manipulate the neurons that trigger hedonic eating. The next step, he says, is to map out how these neurons respond to different types of food and see what makes them so sensitive. He hopes this collaboration will lead to new strategies for effective anti-obesity therapeutics.

For this study, Li and CSHL Associate Professor Stephen Shea combined their neuroscience expertise with CSHL Professor Tobias Janowitz’s expertise in metabolism and endocrinology. They also collaborated with CSHL Assistant Professor Semir Beyaz, an expert in gut and nutrition research. It’s part of an ongoing, multidisciplinary initiative at CSHL to research the connections between the brain and the body.

Reference: “Neurotensin neurons in the extended amygdala control dietary choice and energy homeostasis” by Alessandro Furlan, Alberto Corona, Sara Boyle, Radhashree Sharma, Rachel Rubino, Jill Habel, Eva Carlotta Gablenz, Jacqueline Giovanniello, Semir Beyaz, Tobias Janowitz, Stephen David Shea and Bo Li, 20 October 2022, Nature Neuroscience.
DOI: 10.1038/s41593-022-01178-3

The study was funded by the European Molecular Biology Organization, the Swedish Research Council, the Charles H. Revson Foundation, the National Institutes of Health, the Feil Family Neuroscience Endowment, Cold Spring Harbor Laboratory and Northwell Health Affiliation, and the German Academic Scholarship Foundation.