Published March 18, 2008; doi:10. 0193-1849/08 $8.Versions of this Article: 294/5/E969 _most recent_ Services Google Scholar PubMed A MODERATE INCREASE IN CARNITINE PALMITOYLTRANSFERASE 1A ACTIVITY IS SUFFICIENT TO SUBSTANTIALLY REDUCE HEPATIC TRIGLYCERIDE LEVELS MAJA STEFANOVIC-RACIC,1 GERMAN PERDOMO,1 BENJAMIN S.J.NICHOLAS F.AND ROBERT M._ 1Department of Medicine, Division of Endocrinology and 2Department of Molecular Genetics and Biochemistry, University of Pittsburgh, and 3University of Pittsburgh/Carnegie Mellon University Medical Scientist Training Program, Pittsburgh, Pennsylvania _ Submitted 31 July 2007 ; accepted in final form 17 March 2008 Nonalcoholic fatty liver disease (NAFLD), hypertriglyceridemia, and elevated free fatty acids are present in the majority of patients with metabolic syndrome and type 2 diabetes mellitus and are strongly associated with hepatic insulin resistance.The current study, we tested the hypothesis that an increased rate of fatty acid oxidation in liver would prevent the potentially harmful effects of fatty acid elevation, including hepatic triglyceride (TG) accumulation and elevated TG secretion.Rat hepatocytes were transduced with adenovirus encoding carnitine palmitoyltransferase 1a (Adv-CPT-1a) or control adenoviruses encoding either -galactosidase (Advgal) or carnitine palmitoyltransferase 2 (Adv-CPT-2).Of CPT-1a increased the rate of -oxidation and ketogenesis by 70%, whereas esterification of exogenous fatty acids and de novo lipogenesis were unchanged.CPT-1a overexpression was apanied by a 35% reduction in TG accumulation and a 60% decrease in TG secretion by hepatocytes.Were no changes in secretion of apolipoprotein B (apoB), suggesting the synthesis of smaller, less atherogenic VLDL particles.Evaluate the effect of increasing hepatic CPT-1a activity in vivo, we injected lean or obese male rats with Adv-CPT-1a, Advgal, or Adv-CPT-2.CPT-1a activity was increased by 46%, and the rate of fatty acid oxidation was increased by 44% in lean and 36% in obese CPT-1a-overexpressing animalspared with Adv-CPT-2- or Advgal-treated rats.To observations in vitro, liver TG content was reduced by 37% (lean) and 69% (obese) by this in vivo intervention.Conclude that a moderate stimulation of fatty acid oxidation achieved by an increase in CPT-1a activity is sufficient to substantially reduce hepatic TG accumulation both in vitro and in vivo.Interventions that increase CPT-1a activity could have potential benefits in the treatment of NAFLD.Fatty liver Address for reprint requests and other correspondence: M.Read more Brave-3 questions value of abciximab in pci for heart attack
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