Abstract
Non-alcoholic fatty liver disease (NAFLD) is becoming an increasingly prevalent chronic liver disease all over the world. The present study was undertaken to explore the synergistic effects of sea cucumber saponins (SCS) and eicosapentaenoic acid-enriched phospholipids (EPA-PL) at ratios of 0.5 : 0.5 and 1 : 1 on NAFLD and demonstrate possible protective mechanisms. It was found that the combination of EPA-PL and SCS at half dose exhibited better effects than EPA-PL or SCS alone and the combination of EPA-PL and SCS at full dose in alleviating orotic acid (OA)-induced symptoms including growth parameters, serum parameters and liver function. Further evaluation of the mechanism illustrated that EPA-PL and SCS combination at the ratio of 0.5 : 0.5 could markedly reduce the mRNA expressions of fatty acid synthase, acetyl-CoA carboxylase, glucose-6-phosphate dehydrogenase and malic enzyme genes and significantly increase expression of genes relevant to fatty acid β-oxidation including peroxisome proliferator-activated receptor and its target genes (CPT1, CPT2 and ACOX1), suggesting that the protection of the EPA-PL and SCS combination at the ratio of 0.5 : 0.5 against OA-induced NAFLD might be mainly via lipogenesis inhibition and β-oxidation enhancement in the liver. The synergistic effects of EPA-PL and SCS make it possible to reduce the doses of EPA-PL or SCS to avoid side effects, which is of value for the development of dietary supplements or functional foods for preventing or treating NAFLD.
Highlights
Non-alcoholic fatty liver disease (NAFLD) is a type of fatty liver in the presence of hepatic steatosis and in the absence of alcohol consumption
The treatment of full dose combination of EPA-PL and Sea cucumber saponin (SCS) could significantly suppress the mRNA level of SREBP-1c, which nearly achieved the effect of the control group
The combination of EPA-PL and SCS inhibited the mRNA expression of acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), malic enzyme (ME) and glucose-6-phosphate dehydrogenase (G6PDH) by directly reducing SREBP-1c expression, which could result in the inhibition of hepatic endogenous fatty acid synthesis
Summary
Non-alcoholic fatty liver disease (NAFLD) is a type of fatty liver in the presence of hepatic steatosis and in the absence of alcohol consumption. It is necessary to find functional foods or dietary supplements to prevent or treat non-alcoholic fatty liver. Sea cucumber is a conventional tonic in China, and it contains a wide variety of bioactive compounds such as polysaccharides, saponins and phospholipids [4]. Growing evidence shows that dietary sea cucumber could improve liver function [1,5]. Sea cucumber saponin (SCS), as a kind of marine bioactive substance, has been proved to exhibit significant effects on alleviating insulin resistance [8], lowering lipid accumulation by enhancing β-oxidation via PPARα activation [9] and repressing lipase activity to increase fatty acid excretion in the faeces [10]
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