Signal Transducers Regulating Dietary and Pharmacological BCAA Restriction in Obesity and Type II Diabetes: The Role of Mitochondrial BCAA Carrier Slc25a44

At a Glance

Obesity and type 2 diabetes (T2D) are major public health challenges, with impaired branched-chain amino acid (BCAA) metabolism playing a key role. Restricting dietary BCAAs or using the FDA-approved drug 4-PBA improves body composition, glucose control and lifespan in animal models. Exercise is also critical for weigh loss and maintaining muscle mass, but its interaction with BCAA-targeted interventions is unknown. This project will test whether dietary BCAA restriction, 4-PBA, and exercise—alone or in combination—reverse obesity and improve metabolic health in mice. Using genetic knockout models, it will also determine whether these benefits depend on the mitochondrial BCAA carrier Slc25a44. Findings will provide insights into diet- and drug-based strategies that can be paired with exercise to combat obesity and T2D. By focusing on accessible interventions, the study has the potential to promote health equity in communities disproportionately affected by metabolic disease.