PPARɑ variant V227A reduces plasma triglycerides through enhanced lipoprotein lipolysis.

ABSTRACT: Human single nucleotide variants in peroxisome proliferator-activated receptor-ɑ (PPARɑ) have been associated with beneficial metabolic phenotypes, yet their specific effects on metabolic gene expression are not well defined. Here, we developed a mouse model of a human PPARɑ variant encoding a substitution of valine for alanine at position 227 (V227A) to explore the role of this variant on systemic metabolism. Substitution with this variant in mice reduced plasma triglycerides, without altering body mass or liver lipid accumulation, consistent with phenotypes observed in human cohorts. Gene expression analysis revealed that the V227A variant enhances Ppara target gene expression in mouse liver, consistent with the effects of synthetic PPARɑ agonist treatment. Notably, V227A increased hepat

SUBMITTER: Uchiyama LF 

PROVIDER: S-EPMC12144439 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature