Lipid deprivation amplifies type I IFN responses in monocytes through prenylation: insights from familial combined hypolipidemia type 2.

ABSTRACT: Familial Combined Hypolipidemia (FHBL2) is a genetic disorder caused by loss-of-function mutations in the Angiopoietin-like 3 (ANGPTL3) gene. FHBL2 subjects exhibit hypolipidemia and protection from atherosclerotic cardiovascular diseases. Here, we explored the hypothesis that immunometabolic events contribute to this atheroprotective phenotype. To this aim, circulating monocytes from FHBL2 subjects and controls were profiled through gene expression and phenotypic analysis in vivo and ex vivo. In parallel, immune responses were analyzed in monocytes that were lipid-deprived in vitro. In FHBL2 subjects, leukocytes exhibited lower content of intracellular lipids, together with a spontaneous type I IFN signature in vivo and higher sensitivity to IFN stimulation ex vivo. Lipid restriction in v

SUBMITTER: Pinzon Grimaldos A 

PROVIDER: S-EPMC12764162 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature