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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.

SUBMITTER: Mollica MP

PROVIDER: S-EPMC3995462 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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c9,t11-Conjugated linoleic acid ameliorates steatosis by modulating mitochondrial uncoupling and Nrf2 pathway.

Mollica Maria Pina MP Trinchese Giovanna G Cavaliere Gina G De Filippo Chiara C Cocca Ennio E Gaita Marcello M Della-Gatta Antonio A Marano Angela A Mazzarella Giuseppe G Bergamo Paolo P

Journal of lipid research 20140315 5

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 isomer ...[more]

PMID: 24634500

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Project description:Cis-9, trans-11-conjugated linoleic acid (c9, t11-CLA), a functional fatty acid, is one of the research hotspots in the fields of functional dairy products development because of its multiple beneficial effects in humans and animals. In milk, most c9, t11-CLA is de novo synthesized from trans-11-octadecenoic acid (TVA) and it is confirmed that genes such as stearoyl-coA desaturase 1 (SCD1) play a key role in the synthesis. However, few studies have been reported to deeply elucidate the SCD1-dependent molecular mechanism of cis9, trans11-CLA synthesis and its relationship with the pathways of energy metabolism and lipid metabolism. Therefore, in the present study, MAC-T cells were divided into three groups: CAY group (SCD1-inhibited MAC-T cell model with the addition of CAY, TVA), TVA group (only TVA), and Control group (without CAY, TVA). The relative mRNA expression of SCD1 was measured using real-time PCR, while TVA accumulation and c9, t11 -CLA synthesis were analyzed using gas chromatography (GC). The SCD1-related proteins were firstly screened in MAC-T cells by Tandem Mass Tag (TMT)-based quantitative proteomics analysis, then their functions were annotated by bioinformatic analysis, and finally their relationships with SCD1 were evaluated by parallel reaction monitoring (PRM) analysis and small RNA interference. The results showed that the deficiency of SCD1 led by CAY10566 blocked the synthesis of c9, t11-CLA in MAC-T cells. Sixty-one SCD1-associated proteins were screened and found to be mainly involved in the pathways of energy metabolism and lipid metabolism, such as glycolytic pathway, pentose phosphate pathway, fatty acid elongation pathway, and unsaturated fatty acid biosynthesis. Among these genes, 17 proteins were validated under the PRM analysis. PGAM1 (phosphoglycerate mutase 1), TPI1 (triosephosphate isomerase 1), LDHB (lactate dehydrogenase B), and ALDOA (aldolase, fructose-bisphosphate A) were verified to have a negative relationships with SCD1. This study furthered our understanding of the molecular mechanisms of c9, t11-CLA synthesis in the mammary glands of dairy cows.

Dataset Information

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

Publications

c9,t11-Conjugated linoleic acid ameliorates steatosis by modulating mitochondrial uncoupling and Nrf2 pathway.

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