S-allyl cysteine attenuates free fatty acid-induced lipogenesis in human HepG2 cells through activation of the AMP-activated protein kinase-dependent pathway

Abstract

S-Allyl cysteine (SAC), a nontoxic garlic compound, has a variety of pharmacological properties, including antioxidant and hepatoprotective properties. In this report, we provide evidence that SAC prevented free fatty acid (FFA)-induced lipid accumulation and lipotoxicity in hepatocytes. SAC significantly reduced FFA-induced generation of reactive oxygen species, caspase activation and subsequent cell death. Also, SAC mitigated total cellular lipid and triglyceride accumulation in steatotic HepG2 cells. SAC significantly increased the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in HepG2 cells. Additionally, SAC down-regulated the levels of sterol regulatory element binding protein-1 (SREBP-1) and its target genes, including ACC and fatty acid synthase. Use of a specific inhibitor showed that SAC activated AMPK via calcium/calmodulin-dependent kinase kinase (CaMKK) and silent information regulator T1. Our results demonstrate that SAC activates AMPK through CaMKK and inhibits SREBP-1-mediated hepatic lipogenesis. Therefore, SAC has therapeutic potential for preventing nonalcoholic fatty liver disease.

Keywords: 3-hydroxy-3-methylglutaryl CoA reductase; 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside; AICAR; AMP-activated protein kinase; AMPK; CaMKK; FAS; FFA; HMGCR; Lipogenesis; NAFLD; Nonalcoholic fatty liver disease; ROS; S-Allyl cysteine; S-allyl cysteine; SAC; SREBP-1; Steatosis; TG; calcium/calmodulin-dependent kinase kinase; fatty acid synthase; free fatty acid; nonalcoholic fatty liver disease; reactive oxygen species; sterol regulatory element binding protein-1; triglyceride.