title: Niacin inhibits fat accumulation, oxidative stress, and inflammatory cytokine IL-8 in cultured hepatocytes: Impact on non-alcoholic fatty liver disease.
abstract: OBJECTIVE
  Non-alcoholic fatty liver disease (NAFLD) is a common disorder characterized by excessive hepatic fat accumulation, production of reactive oxygen species (ROS), inflammation and potentially resulting in non-alcoholic steatohepatitis (NASH), cirrhosis and end-stage liver disease. Recently, we have shown that niacin significantly prevented hepatic steatosis and regressed pre-existing steatosis in high-fat fed rat model of NAFLD. To gain further insight into the cellular mechanisms, this study investigated the effect of niacin on human hepatocyte fat accumulation, ROS production, and inflammatory mediator IL-8 secretion.
  
  
  METHODS
  Human hepatoblastoma cell line HepG2 or human primary hepatocytes were first stimulated with palmitic acid followed by treatment with niacin or control for 24 h.
  
  
  RESULTS
  The data indicated that niacin (at 0.25 and 0.5 mmol/L doses) significantly inhibited palmitic acid-induced fat accumulation in human hepatocytes by 45-62%. This effect was associated with inhibition of diacylglycerol acyltransferase 2 (DGAT2) mRNA expression without affecting the mRNA expression of fatty acid synthase (FAS) and carnitine palmitoyltransferase 1 (CPT1). Niacin attenuated hepatocyte ROS production and it also inhibited NADPH oxidase activity. Niacin reduced palmitic acid-induced IL-8 levels.
  
  
  CONCLUSIONS
  These findings suggest that niacin, through inhibiting hepatocyte DGAT2 and NADPH oxidase activity, attenuates hepatic fat accumulation and ROS production respectively. Decreased ROS production, at least in part, may have contributed to the inhibition of pro-inflammatory IL-8 levels. These mechanistic studies may be useful for the clinical development of niacin and niacin-related compounds for the treatment of NAFLD/NASH and its complications.
authors.affiliation: Department of Veterans Affairs Healthcare System, Long Beach, CA; University of California, Irvine, CA.
authors.forename: Shobha H
authors.initials: SH
authors.lastname: Ganji
authors.affiliation: Department of Veterans Affairs Healthcare System, Long Beach, CA; University of California, Irvine, CA.
authors.forename: Moti L
authors.initials: ML
authors.lastname: Kashyap
authors.affiliation: Department of Veterans Affairs Healthcare System, Long Beach, CA; University of California, Irvine, CA. Electronic address: vaijinath.kamanna@va.gov.
authors.forename: Vaijinath S
authors.initials: VS
authors.lastname: Kamanna
mesh_terms: D051048:Diacylglycerol O-Acyltransferase / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D016209:Interleukin-8 / Q000378:metabolism*; D050356:Lipid Metabolism / Q000187:drug effects*; D009525:Niacin / Q000494:pharmacology*; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy* / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D019308:Palmitic Acid / Q000494:pharmacology; D061251:Primary Cell Culture; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000960:Hypolipidemic Agents; D016209:Interleukin-8; D017382:Reactive Oxygen Species; D009525:Niacin; D019308:Palmitic Acid; C494885:DGAT2 protein, human; D051048:Diacylglycerol O-Acyltransferase
keywords: Hepatic inflammation; Nicotinic acid; Non-alcoholic steatohepatitis; Steatosis