IL-1R-IRAKM-Slc25a1 signaling axis reprograms lipogenesis in adipocytes to promote diet-induced obesity in mice.

ABSTRACT: Toll-like receptors/Interleukin-1 receptor signaling plays an important role in high-fat diet-induced adipose tissue dysfunction contributing to obesity-associated metabolic syndromes. Here, we show an unconventional IL-1R-IRAKM-Slc25a1 signaling axis in adipocytes that reprograms lipogenesis to promote diet-induced obesity. Adipocyte-specific deficiency of IRAKM reduces high-fat diet-induced body weight gain, increases whole body energy expenditure and improves insulin resistance, associated with decreased lipid accumulation and adipocyte cell sizes. IL-1β stimulation induces the translocation of IRAKM Myddosome to mitochondria to promote de novo lipogenesis in adipocytes. Mechanistically, IRAKM interacts with and phosphorylates mitochondrial citrate carrier Slc25a1 to promote IL-1β-indu

SUBMITTER: Liu W 

PROVIDER: S-EPMC9117277 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature