title: Lipoic acid administration prevents nonalcoholic steatosis linked to long-term high-fat feeding by modulating mitochondrial function.
abstract: Nonalcoholic steatosis is an important hepatic complication of obesity linked to mitochondrial dysfunction and insulin resistance. Furthermore, lipoic acid has been reported to have beneficial effects on mitochondrial function. In this study, we analyzed the potential protective effect of lipoic acid supplementation against the development of nonalcoholic steatosis associated with a long-term high-fat diet feeding and the potential mechanism of this effect. Wistar rats were fed on a standard diet (n=10), a high-fat diet (n=10) and a high-fat diet supplemented with lipoic acid (n=10). A group pair-fed to the latter group (n=6) was also included. Lipoic acid prevented hepatic triglyceride accumulation and liver damage in rats fed a high-fat diet (-68%±11.3% vs. obese group) through the modulation of genes involved in lipogenesis and mitochondrial β-oxidation and by improving insulin sensitivity. Moreover, this molecule showed an inhibitory action on electron transport chain complexes activities (P<.01-P<.001) and adenosine triphosphate synthesis (P<.05), and reduced significantly energy efficiency. By contrast, lipoic acid induced an increase in mitochondrial copy number and in Ucp2 gene expression (P<.001 vs. obese). In summary, this investigation demonstrated the ability of lipoic acid to prevent nonalcoholic steatosis induced by a high-fat intake. Finally, the novelty and importance of this study are the finding of how lipoic acid modulates some of the mitochondrial processes involved in energy homeostasis. The reduction in mitochondrial energy efficiency could also explain, at least in part, the beneficial effects of lipoic acid not only in fatty liver but also in preventing excessive body weight gain.
authors.affiliation: Department of Nutrition, Food Science, Physiology and Toxicology, University of Navarra, 31008 Pamplona, Spain.
authors.forename: M Pilar
authors.initials: MP
authors.lastname: Valdecantos
authors.forename: Patricia
authors.initials: P
authors.lastname: Pérez-Matute
authors.forename: Pedro
authors.initials: P
authors.lastname: González-Muniesa
authors.forename: Pedro L
authors.initials: PL
authors.lastname: Prieto-Hontoria
authors.forename: María J
authors.initials: MJ
authors.lastname: Moreno-Aliaga
authors.forename: J Alfredo
authors.initials: JA
authors.lastname: Martínez
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002952:Citric Acid Cycle / Q000187:drug effects; D059305:Diet, High-Fat / Q000009:adverse effects*; D004798:Enzymes / Q000378:metabolism; D005234:Fatty Liver / Q000209:etiology / Q000517:prevention & control*; D005786:Gene Expression Regulation / Q000187:drug effects; D007328:Insulin / Q000097:blood; D007473:Ion Channels / Q000235:genetics; D050356:Lipid Metabolism / Q000187:drug effects; D050155:Lipogenesis / Q000187:drug effects / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics; D009929:Organ Size / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D008063:Thioctic Acid / Q000494:pharmacology*; D000637:Transaminases / Q000097:blood; D014280:Triglycerides / Q000378:metabolism; D000071246:Uncoupling Protein 2
chemical_list: D001786:Blood Glucose; D004798:Enzymes; D007328:Insulin; D007473:Ion Channels; D024101:Mitochondrial Proteins; D020011:Protective Agents; D014280:Triglycerides; C000604391:Ucp2 protein, rat; D000071246:Uncoupling Protein 2; D008063:Thioctic Acid; D000255:Adenosine Triphosphate; D000637:Transaminases