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Gene Linked to Obesity Has Role in Different Types of Human Behavior

Researchers discovered that a gene with a known role in obesity also plays an unexpected role in human behavior. The gene, called SH2B1, is a key regulator of leptin sensitivity in mice; leptin is a hormone that suppresses appetite. Previous research showed that mice lacking the SH2B1 gene have impaired leptin and insulin signaling, making them severely obese and insulin resistant. To investigate the role of SH2B1 in human metabolism, scientists examined whether obese people had mutations in their SH2B1 gene. They studied people with severe early‑onset obesity (developed before age 10) who also had higher than expected levels of insulin resistance for their weight. They identified four different types of mutations in the SH2B1 gene that were not found in people who are normal weight. The mutations were inherited from their overweight or obese parents. The people with these mutations had excessive appetites and at adulthood were a shorter height than average. A surprising finding was that they also had behavioral abnormalities, as reported by their families and health care providers. These abnormalities included delayed speech and language development, aggressive behavior, and a tendency toward social isolation. Further experiments showed that some of the identified mutations impaired leptin signaling while others did not, suggesting that the SH2B1 protein may be exerting some of its effects through cellular pathways that are independent of leptin. This research sheds new light on the human SH2B1 gene and suggests that it not only plays a role in obesity, but may also be an important factor in controlling certain types of human behavior.


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