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Enhanced amelioration of high-fat diet-induced fatty liver by docosahexaenoic acid and lysine supplementations.

ABSTRACT: Fatty liver disease is the most common pathological condition in the liver. Here, we generated high-fat diet-(HFD-) induced nonalcoholic fatty liver disease (NAFLD) in mice and tested the effects of docosahexaenoic acid (DHA) and lysine during a four-week regular chow (RC)feeding. Our results showed that 1% lysine and the combination of 1% lysine + 1% DHA reduced body weight. Moreover, serum triglyceride levels were reduced by 1% DHA and 1% lysine, whereas serum alanine transaminase activity was reduced by 1% DHA and 1% DHA + 0.5% lysine. Switching to RC reduced hepatic lipid droplet accumulation, which was further reduced by the addition of DHA or lysine. Furthermore, the mRNA expressions of hepatic proinflammatory cytokines were suppressed by DHA and combinations of DHA + lysine, whereas the mRNA for the lipogenic gene, acetyl-CoA carboxylase 1 (ACC1), was suppressed by DHA. In the gonadal adipose tissues, combinations of DHA and lysine inhibited mRNA expression of lipid metabolism-associated genes, including ACC1, fatty acid synthase, lipoprotein lipase, and perilipin. In conclusion, the present study demonstrated that, in conjunction with RC-induced benefits, supplementation with DHA or lysine further ameliorated the high-fat diet-induced NAFLD and provided an alternative strategy to treat, and potentially prevent, NAFLD.

SUBMITTER: Lin HY

PROVIDER: S-EPMC4055637 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Enhanced amelioration of high-fat diet-induced fatty liver by docosahexaenoic acid and lysine supplementations.

Lin Hsin-Yu HY Chen Chih-Chien CC Chen Yu-Jen YJ Lin Yuan-Yu YY Mersmann Harry J HJ Ding Shih-Torng ST

BioMed research international 20140525

Fatty liver disease is the most common pathological condition in the liver. Here, we generated high-fat diet-(HFD-) induced nonalcoholic fatty liver disease (NAFLD) in mice and tested the effects of docosahexaenoic acid (DHA) and lysine during a four-week regular chow (RC)feeding. Our results showed that 1% lysine and the combination of 1% lysine + 1% DHA reduced body weight. Moreover, serum triglyceride levels were reduced by 1% DHA and 1% lysine, whereas serum alanine transaminase activity was ...[more]

PMID: 24967351

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Project description:IntroductionNonalcoholic fatty liver disease (NAFLD) is one of the most important causes of liver-related morbidity and mortality in children. Recently, we have reported the effects of docosahexaenoic acid (DHA), the major dietary long-chain polyunsaturated fatty acids, in children with NAFLD. DHA exerts a potent anti-inflammatory activity through the G protein-coupled receptor (GPR)120. Our aim was to investigate in pediatric NAFLD the mechanisms underlying the effects of DHA administration on histo-pathological aspects, GPR120 expression, hepatic progenitor cell activation and macrophage pool.Patients and methods20 children with untreated NAFLD were included. Children were treated with DHA for 18 months. Liver biopsies before and after the treatment were analyzed. Hepatic progenitor cell activation, macrophage pool and GPR120 expression were evaluated and correlated with clinical and histo-pathological parameters.ResultsGPR120 was expressed by hepatocytes, liver macrophages, and hepatic progenitor cells. After DHA treatment, the following modifications were present: i) the improvement of histo-pathological parameters such as NAFLD activity score, ballooning, and steatosis; ii) the reduction of hepatic progenitor cell activation in correlation with histo-pathological parameters; iii) the reduction of the number of inflammatory macrophages; iv) the increase of GPR120 expression in hepatocytes; v) the reduction of serine-311-phosphorylated nuclear factor kappa B (NF-κB) nuclear translocation in hepatocytes and macrophages in correlation with serum inflammatory cytokines.ConclusionsDHA could modulate hepatic progenitor cell activation, hepatocyte survival and macrophage polarization through the interaction with GPR120 and NF-κB repression. In this scenario, the modulation of GPR120 exploits a novel crucial role in the regulation of the cell-to-cell cross-talk that drives inflammatory response, hepatic progenitor cell activation and hepatocyte survival.

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Enhanced amelioration of high-fat diet-induced fatty liver by docosahexaenoic acid and lysine supplementations.

Publications

Enhanced amelioration of high-fat diet-induced fatty liver by docosahexaenoic acid and lysine supplementations.

Similar Datasets

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