PPA1 Regulates Systemic Insulin Sensitivity by Maintaining Adipocyte Mitochondria Function as a Novel PPARγ Target Gene

Downregulation of mitochondrial function in adipose tissue is considered as one important driver for the development obesity-associated metabolic disorders. Inorganic pyrophosphatase 1 (PPA1) an enzyme that catalyzes hydrolysis inorganic pyrophosphate to phosphate and required anabolism take place cells. Although alteration PPA1 has been related some diseases, importance syndromes never discussed. In this study, we found global knockout mice (PPA1+/–) showed impaired glucose tolerance severe insulin resistance under high-fat-diet feeding. addition, ectopic lipid accumulation were observed. Conversely, overexpression by adeno-associated virus injection can partly reverse disorders PPA1+/– mice, suggesting responsible observed mice. Mechanistic studies revealed acted a PPARγ target gene maintain adipocytes. Furthermore, specific knockdown fat body Drosophila led mitochondria morphology, decreased storage, made more sensitive starvation. conclusion, first time, our findings demonstrate maintaining whole-body homeostasis.