Hepatic ENTPD5 Is Critical for Maintaining Metabolic Homeostasis and Promoting Brown Adipose Tissue Thermogenesis.

ABSTRACT: Although hepatocyte-released adenosine triphosphate (ATP) plays important roles in maintaining metabolic homeostasis, how its hydrolyzation outside hepatocytes impacts on glucolipid metabolism remains unclear. The authors aim to identify the enzyme(s) that hydrolyzes hepatocyte-secreted ATP to regulate metabolic homeostasis. All known ATP-hydrolyzing enzymes are expressed with the highest expression of ectonucleoside triphosphate diphosphohydrolase 5 (ENTPD5) in hepatocytes. ENTPD5 expression is reduced in steatotic mouse and human livers. Hepatic ENTPD5 overexpression ameliorates the deregulated glucolipid metabolism and obesity with increased brown adipose tissue (BAT) thermogenesis, while hepatic ENTPD5 silencing exerted the opposite effects in obese mice. Mechanistically, ENTPD5 hydrol

SUBMITTER: Ma R 

PROVIDER: S-EPMC12561356 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature