7-dehydrocholesterol promotes CCL2-secretion from porcine skeletal muscle satellite cells, enhancing the migration of preadipocytes

Abstract

The adipose tissue deposited in skeletal muscle is referred to as intramuscular fat (IMF). In animal husbandry, regulating the content of IMF contributes to the production of meat products with desirable flavor. In human medicine, IMF is often associated with metabolic dysregulation. Here, we discovered endogenous 7-dehydrocholesterol (7-DHC) in muscle primarily affects the secretion of the chemokine C-C motif ligand 2 (CCL2) by skeletal muscle satellite cells (MuSCs). CCL2 induced by 7-DHC promotes the migration of preadipocytes co-cultured with MuSCs. An imbalance in cholesterol metabolism homeostasis in 7-DHC treated MuSCs was identified by bulk RNA-Seq. Further, 7-DHC treatment resulted in a decrease in intracellular cholesterol content due to increased cholesterol efflux. Mechanistically, 7-DHC downregulated ACAT2 expression, and inhibition of ACAT2 enhanced CCL2 secretion of MuSCs and preadipocytes migration in co-cultured system. These findings reveal a novel role of 7-DHC in linking cholesterol homeostasis to CCL2-mediated preadipocytes recruitment, providing insights into the regulation of IMF deposition and potential strategies for improving meat quality and muscle regeneration.

Keywords: 7-Dehydrocholesterol; CCL2; Cholesterol metabolism; Migration; Preadipocytes; Skeletal muscle satellite cells.