Area: Pediatrics, Molecular and Human Genetics
Dr. Yong Xu is associate professor of pediatrics and of molecular and cellular biology. His lab investigates how neurons in the hypothalamus regulate appetite and satiety in mammals, issues associated with current important public health concerns, such as obesity, diabetes and eating disorders.
Dr. Xu’s work published in Nature Medicine in 2017 investigated a rare human disease, neonatal progeroid syndrome (NPS), which is characterized by loss of appetite and extreme leanness. NPS patients carry mutations that result in the loss of a blood circulating factor, a novel hunger hormone called asprosin. The researchers identified asprosin’s mechanism of action showing that it activates appetite-stimulating AgRP neurons and deactivates appetite-suppressing POMC neurons in the hypothalamus, which results in increased appetite.This work also provided a potential treatment strategy (asprosin supplement) and highlighted the possibility that asprosin-neutralizing approaches might help manage obesity.
Dr. Xu’s paper in Nature Communications (2018) revealed a completely new perspective on gender differences in body weight control. When male and female mice eat the same high-fat diet, the males gain significantly more weight than the females.Dr. Xu studied the POMC neurons in the hypothalamus, known to help maintain normal body weight. His lab compared the firing rate of electrical signals‒ a measure of how neurons communicate‒ between POMC neurons in males and females. They found that female POMC neurons normally fire faster than male neurons and this was associated with higher levels of expression of gene TAp63.
In 2019, Dr. Xu’s lab revealed in Nature Communications another piece of the complex puzzle of body weight control, this time showing a role for steroid receptor coactivator-1 (SRC-1)‒a protein a known to participate in the regulation of body weight, but whose precise role is not clear.They discovered that SRC-1 is highly expressed in POMC murine neurons in the hypothalamus and affects how these neurons regulate appetite. In collaboration with University of Cambridge’s Dr. I. Sadaf Farooqi, the team identified a group of severely obese children carrying rare genetic variants in the SRC-1 gene that produce dysfunctional proteins. Mice genetically engineered to express one of the human SRC-1 genetic variants found in obese children ate more and gained weight. This is the first report of SRC-1 playing a role in the hypothalamus in the context of body weight control.