Adenylosuccinate Synthase 1 Deficiency Improves Energy Metabolism by Promoting Adipose Tissue Re-esterification via Glycerol Kinase Upregulation.

ABSTRACT: Purine metabolism enzymes have a well-established role in maintaining the nucleotide pool, thereby sustaining cellular energy homeostasis. Although reduced purine nucleotide concentrations have been reported can influence uncoupling protein 1 (UCP1)activity in thermogenic adipocytes, our study identifies adenylosuccinate synthase 1 (Adss1), an enzyme in de novo purine biosynthesis, as a critical regulator of metabolic remodeling in inguinal white adipose tissue (iWAT) through a mechanism distinct from UCP1 activity. Adipose-specific Adss1 knockout mice showed increased energy expenditure and resistance to diet-induced obesity with improved metabolic dysfunction. Loss of Adss1 upregulates glycerol kinase (Gk) expression, thereby stimulating glycerol-dependent fatty acid re-esterification in

SUBMITTER: Sun J 

PROVIDER: S-EPMC12767003 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature