DOI: 10.1152/ajpendo.00262.2026 ISSN: 0193-1849
Adipocyte lipolysis is a determinant of skeletal muscle size during fasting and feeding
Daniel M. Marko, Rhea V. Vemula, Meghan O. Conn, Nazli Robin, Angela M. Schmidt, Irena A. Rebalka, Jonathan D. SchertzerThis study demonstrates that adipocyte ATGL is a critical regulator of adipose-muscle metabolic crosstalk. Limiting adipocyte lipolysis through adipose ATGL deletion reduced blood lipid and ketone fuel availability, thereby increasing adipose retention, decreasing skeletal muscle mass and fiber size, and increasing muscle atrogene expression, particularly during intermittent fasting. These findings support a model in which impaired adipocyte lipid mobilization shifts whole body energy demands away from adipose and toward skeletal muscle, promoting muscle catabolism during fasting.