Sestrin2 Regulates Beneficial? 3-Adrenergic Receptor- Mediated Effects Observed in Inguinal White Adipose Tissue and Soleus Muscle

Sestrin2, a well-known adenosine monophosphate-activated protein kinase (AMPK) regulator, plays a protective role against metabolic stress. The f33-adrenergic receptor (f33AR) induces fat browning and inhibits muscle atrophy in an AMPK-dependent manner. However, no prior research has examined the relationship of sestrin2 with f33AR in body composition changes. In this study, CL 316,243 (CL), a f33AR agonist, was administered to wild-type and sestrin2-knockout (KO) mice for 2 weeks, and fat and muscle tissues were harvested. CL induced AMPK phosphorylation, expression of brown-fat markers, and mitochondrial biogenesis, which resulted in the reduction of lipid droplet size in inguinal white adipose tissue (iWAT). These effects were not observed in sestrin2KO mice. In CL-treated soleus muscle, sestrin2-KO was related to decreased myogenic gene expression and increased levels of muscle atrophy-related molecules. Our results suggest that sestrin2 is associated with beneficial f33AR-mediated changes in body composition, especially in iWAT and in the soleus.