IBBR publication #609

C9, t11-Conjugated linoleic acid ameliorates steatosis by modulating mitochondrial uncoupling and Nrf2 pathway

Mollica Mp, Trinchese G, Cavaliere G, De Filippo C, Cocca E, Gaita M, Della-gatta A, Marano A, Mazzarella G, Bergamo P

Journal of lipid research American Society for Biochemistry and Molecular Biology Paese di pubblicazione: Stati Uniti d’America Lingua: inglese ISSN: 0022-2275 55 (5): 837-849. (2014)
doi: 10.1194/jlr.M044032

Oxidative stress, hepatic steatosis, and mitochondrial dysfunction are key pathophysiological features of nonalcoholic fatty liver disease. A conjugated linoleic acid (CLA) mixture of cis 9, trans 11 (9,11-CLA) and trans 10, cis 12 (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.-Mollica, M. P., G. Trinchese, G. Cavaliere, C. De Filippo, E. Cocca, M. Gaita, A. Della-Gatta, A. Marano, G. Mazzarella, and P. Bergamo. c 9, t 11-Conjugated linoleic acid ameliorates steatosis by modulating mitochondrial uncoupling and Nrf2 pathway. J. Lipid Res . 2014. 55: 837-849. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.