Electroacupuncture regulates hepatic cholesterol synthesis by HMGCR deubiquitination in rats

This experiment was designed to explore the effect and mechanism of electroacupuncture (EA) for hyperlipidemia and hepatic cholesterol synthesis in rats. Liver and adipose tissues were assessed histologically, and body and liver weight, serum and liver lipid levels, expression of mTOR/ubiquitin-specific peptidase 20 (USP20)/recombinant 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), and phosphorylation of mTOR and USP20 were measured. In vitro deubiquitination assays with liver cytosol were conducted. EA at Fenglong point ameliorated hyperlipidemia and hepatocyte steatosis, and decreased p-USP20, p-mTOR and HMGCR expression in the liver by reducing deubiquitination. Furthermore, EA decreased feeding-induced lipid biosynthesis in the liver. Concomitantly, EA prevented the induction of phosphorylated USP20 and mTOR, and HMGCR expression; and reduced the deubiquitination of HMGCR after re-feeding. This experiment demonstrated that EA can effectively improve hyperlipidemia and reduce hepatic cholesterol synthesis by counteracting the deubiquitination activity of HMGCR in hyperlipidemic rats.