Peroxisomal metabolism of branched fatty acids regulates energy homeostasis.

ABSTRACT: Brown and beige adipocytes express uncoupling protein 1 (UCP1), a mitochondrial protein that dissociates respiration from ATP synthesis and promotes heat production and energy expenditure. However, UCP1^-/- mice are not obese^1-5, consistent with the existence of alternative mechanisms of thermogenesis^6-8. Here we describe a UCP1-independent mechanism of thermogenesis involving ATP-consuming metabolism of monomethyl branched-chain fatty acids (mmBCFA) in peroxisomes. These fatty acids are synthesized by fatty acid synthase using precursors derived from catabolism of branched-chain amino acids⁹ and our results indicate that β-oxidation of mmBCFAs is mediated by the peroxisomal protein acyl-CoA oxidase 2 (ACOX2). Notably, cold exposure upregulated pr

SUBMITTER: Liu X 

PROVIDER: S-EPMC12571886 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature