BCAAs acutely drive glucose dysregulation and insulin resistance: role of AgRP neurons

High-protein diets, often rich in branched-chain amino acids (BCAAs), are associated with obesity and diabetes. This study investigated the acute effects of BCAAs on glucose metabolism and insulin sensitivity in mice. A single BCAA infusion acutely elevated blood glucose and plasma insulin in male mice, with impaired whole-body insulin sensitivity during hyperinsulinemic-euglycemic clamps. Chemogenetic overactivation of AgRP neurons, implicated in obesity, impaired glucose tolerance, normalized by BCAA reduction. These effects were largely sex-specific, primarily observed in males. The findings suggest BCAAs acutely impair glucose homeostasis and insulin sensitivity, potentially explaining their long-term effects in obesity and diabetes, and highlight a novel role for AgRP neurons in BCAA-mediated glucose regulation.

Harsh Shah, Ritchel B. Gannaban, Zobayda Farzana Haque, Fereshteh Dehghani, Alyssa Kramer, Frances Bowers, Matthew Ta, Thy Huynh, Marjan Ramezan, Ashley Maniates, Andrew C. Shin