title: c9,t11-Conjugated linoleic acid ameliorates steatosis by modulating mitochondrial uncoupling and Nrf2 pathway.
abstract: Oxidative stress, hepatic steatosis, and mitochondrial dysfunction are key pathophysiological features of nonalcoholic fatty liver disease. A conjugated linoleic acid (CLA) mixture of cis9,trans11 (9,11-CLA) and trans10,cis12 (10,12-CLA) isomers enhanced the antioxidant/detoxifying mechanism via the activation of nuclear factor E2-related factor-2 (Nrf2) and improved mitochondrial function, but less is known about the actions of specific isomers. The differential ability of individual CLA isomers to modulate these pathways was explored in Wistar rats fed for 4 weeks with a lard-based high-fat diet (L) or with control diet (CD), and, within each dietary treatment, two subgroups were daily administered with 9,11-CLA or 10,12-CLA (30 mg/day). The 9,11-CLA, but not 10,12-CLA, supplementation to CD rats improves the GSH/GSSG ratio in the liver, mitochondrial functions, and Nrf2 activity. Histological examination reveals a reduction of steatosis in L-fed rats supplemented with both CLA isomers, but 9,11-CLA downregulated plasma concentrations of proinflammatory markers, mitochondrial dysfunction, and oxidative stress markers in liver more efficiently than in 10,12-CLA treatment. The present study demonstrates the higher protective effect of 9,11-CLA against diet-induced pro-oxidant and proinflammatory signs and suggests that these effects are determined, at least in part, by its ability to activate the Nrf2 pathway and to improve the mitochondrial functioning and biogenesis.
authors.affiliation: Dipartimento delle Scienze Biologiche, Università degli Studi di Napoli "Federico II," Napoli, Italy.
authors.forename: Maria Pina
authors.initials: MP
authors.lastname: Mollica
authors.forename: Giovanna
authors.initials: G
authors.lastname: Trinchese
authors.forename: Gina
authors.initials: G
authors.lastname: Cavaliere
authors.forename: Chiara
authors.initials: C
authors.lastname: De Filippo
authors.forename: Ennio
authors.initials: E
authors.lastname: Cocca
authors.forename: Marcello
authors.initials: M
authors.lastname: Gaita
authors.forename: Antonio
authors.initials: A
authors.lastname: Della-Gatta
authors.forename: Angela
authors.initials: A
authors.lastname: Marano
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mazzarella
authors.forename: Paolo
authors.initials: P
authors.lastname: Bergamo
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects; D059305:Diet, High-Fat / Q000009:adverse effects; D019587:Dietary Supplements; D005786:Gene Expression Regulation / Q000187:drug effects; D007473:Ion Channels / Q000378:metabolism*; D044243:Linoleic Acids, Conjugated / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D024101:Mitochondrial Proteins / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D065626:Non-alcoholic Fatty Liver Disease / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D000071256:Uncoupling Protein 1
chemical_list: D015415:Biomarkers; D016207:Cytokines; D007473:Ion Channels; D044243:Linoleic Acids, Conjugated; D024101:Mitochondrial Proteins; D051267:NF-E2-Related Factor 2; D000071256:Uncoupling Protein 1
keywords: fatty acids; mitochondrial efficiency; nuclear factor E2-related factor-2