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

Abstract

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 AMPKα expression were inhibited in SAT when ASC level was low. p53 and AMP-activated protein kinase α (AMPKα) 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/AMPKα axis. Regulation of ASC on lipid metabolism might be a novel therapeutic target for obesity.

Aging and homeostasis of the hypodermis in the age-related deterioration of skin function

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Uncoupled pyroptosis and IL-1β secretion downstream of inflammasome signaling

“…In addition to versatile functions in inflammasomeindependent biological processes (195)(196)(197)(198)(199)(200), ASC has established its central role in inflammasome signaling. Briefly, ASC connects the inflammasome sensor and caspase-1 via homotypic interactions of CARD-CARD and PYD-PYD, hierarchically organizing and densely packing the ternary inflammasome complex into a micrometer-sized disk-like structure that is denoted a pyroptosome or an ASC speck.…”