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Research identifies the SH2B1 gene’s critical role in obesity through its impact on brain function and energy regulation, offering promising therapeutic potential for obesity management without the side effects of current drugs like Ozempic. Obesity is a complex condition influenced by genetics, the food environment, behavior, and other factors. Historically, securing enough food to survive was challenging, but today, for most people, it’s as simple as opening a refrigerator.

A gene called SH2B1 has been shown to play an important role in regulating food intake. SH2B1 mutations in people are associated with obesity, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease, formerly known as non-alcoholic fatty liver disease. “This gene controls feeding and energy expenditure.



Obesity is caused by two opposing axes: If you eat too much, you gain fat. Spend too little energy and fat accumulates,” said Liangyou Rui, Ph.D.

, Department of Molecular & Integrative Physiology and the Elizabeth Weiser Caswell Diabetes Institute at the U-M Medical School. A study conducted by Rui and the team identifies where this gene is acting inside the brain, an area called the paraventricular hypothalamus, or PVH, which is involved in regulating blood pressure and fluid balance. Additionally, the team discovered that neurons that express SH2B1 create a circuit, talking to neurons downstream in an area known as the dorsal raphe nucleus, located in the brainstem.

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