CCN1/Integrin α₅β₁ Instigates Free Fatty Acid-Induced Hepatocyte Lipid Accumulation and Pyroptosis through NLRP3 Inflammasome Activation.

ABSTRACT: Hyperlipidemia with high blood levels of free fatty acids (FFA) is the leading cause of non-alcoholic steatohepatitis. CCN1 is a secreted matricellular protein that drives various cellular functions, including proliferation, migration, and differentiation. However, its role in mediating FFA-induced pro-inflammatory cell death and its underlying molecular mechanisms have not been characterized. In this study, we demonstrated that CCN1 was upregulated in the livers of obese mice. The increase in FFA-induced CCN1 was evaluated in vitro by treating hepatocytes with a combination of oleic acid and palmitic acid (2:1). Gene silencing using specific small interfering RNAs (siRNA) revealed that CCN1 participated in FFA-induced intracellular lipid accumulation, caspase-1 activation, and hepatocyte

SUBMITTER: Yao Q 

PROVIDER: S-EPMC9505842 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature