Inflammasome Activation and Pyroptosis via a Lipid-regulated SIRT1-p53-ASC Axis in Macrophages From Male Mice and Humans.

ABSTRACT: Obesity-linked diabetes is associated with accumulation of proinflammatory macrophages into adipose tissue leading to inflammasome activation and pyroptotic secretion of interleukin (IL)-1β and IL-18. Targeting fatty acid binding protein 4 (FABP4) uncouples obesity from inflammation, attenuates characteristics of type 2 diabetes and is mechanistically linked to the cellular accumulation of monounsaturated fatty acids in macrophages. Herein we show that pharmacologic inhibition or genetic deletion of FABP4 activates silent mating type information regulation 2 homolog 1 (SIRT1) and deacetylates its downstream targets p53 and signal transducer and activator of transcription 3 (STAT3). Pharmacologic inhibition of fatty acid synthase or stearoyl-coenzyme A desaturase inhibits, whereas exogenous

SUBMITTER: Huang Y 

PROVIDER: S-EPMC8896164 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature