ASC Regulates Subcutaneous Adipose Tissue Lipogenesis and Lipolysis via p53/AMPKα Axis

Obesity has become an extensive threat to human health due to associated chronic inflammation and metabolic diseases. Apoptosis-associated speck-like protein (ASC) is a critical link between inflammasome and apoptosis-inducing proteins. In this study, we aimed to clarify the role of ASC in lipid metabolism. With high-fat diet (HFD) and knockout leptin gene mice (ob/ob), we found that ASC expression in subcutaneous adipose tissue (SAT) correlated with obesity. It could also positively regulate the reprogramming of cellular energy metabolism. Stromal vascular fractions (SVF) cells derived from the SAT of Asc(-/-) mice or SVF from wild-type (WT) mice transfected with ASC siRNA were used to further investigate the underlying molecular mechanisms. We found ASC deficiency could lead to lipogenesis and inhibit lipolysis in SAT, aggravating lipid accumulation and impairing metabolic balance. In addition, our results showed that p53 and AMPK alpha expression were inhibited in SAT when ASC level was low. p53 and AMP-activated protein kinase alpha (AMPK alpha) were then assessed to elucidate whether they were downstream of ASC in regulating lipid metabolism. Our results revealed that ASC deficiency could promote lipid accumulation by increasing lipogenesis and decreasing lipolysis through p53/AMPK alpha axis. Regulation of ASC on lipid metabolism might be a novel therapeutic target for obesity.

Automated summary

Obesity poses a significant threat to human health due to chronic inflammation and metabolic diseases. Apoptosis-associated speck-like protein (ASC) acts as a critical link between inflammasome and apoptosis-inducing proteins. This study reveals that ASC deficiency promotes lipid accumulation by increasing lipogenesis and decreasing lipolysis in subcutaneous adipose tissue, aggravating obesity and metabolic imbalance. In addition, ASC regulation of p53/AMPKα axis contributes to the dysregulation of lipid metabolism. The findings suggest that ASC could be a potential therapeutic target for obesity.