title: 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.
authors: Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea.
authors: Yong Pil
authors: YP
authors: Hwang
authors: Hyung Gyun
authors: HG
authors: Kim
authors: Jae Ho
authors: JH
authors: Choi
authors: Minh Truong
authors: MT
authors: Do
authors: Young Chul
authors: YC
authors: Chung
authors: Tae Cheon
authors: TC
authors: Jeong
authors: Hye Gwang
authors: HG
authors: Jeong
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D000103:Acetyl-CoA Carboxylase / Q000235:genetics / Q000378:metabolism; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase / Q000235:genetics / Q000378:metabolism; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015536:Down-Regulation; D005230:Fatty Acids, Nonesterified / Q000008:administration & dosage / Q000009:adverse effects*; D005234:Fatty Liver / Q000517:prevention & control; D005737:Garlic / Q000737:chemistry; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D050155:Lipogenesis / Q000187:drug effects*; D065626:Non-alcoholic Fatty Liver Disease; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D005230:Fatty Acids, Nonesterified; D010936:Plant Extracts; D017382:Reactive Oxygen Species; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; C065299:S-allylcysteine; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase; D055372:AMP-Activated Protein Kinases; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D000103:Acetyl-CoA Carboxylase; D003545:Cysteine
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