Eicosapentaenoic Acid‐Enriched Phosphatidylcholine Attenuated Hepatic Steatosis Through Regulation of Cholesterol Metabolism in Rats with Nonalcoholic Fatty Liver Disease
Abstract:Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world. Disturbed cholesterol metabolism plays a crucial role in the development of NAFLD. The present study was conducted to evaluate the effects of EPA-PC extracted from sea cucumber on liver steatosis and cholesterol metabolism in NAFLD. Male Wistar rats were randomly divided into seven groups (normal control group, model group, lovastatin group, low- and high-dose EPA groups, and low- and high-dose EPA-PC groups). Model… Show more
“…Activities of AST and ALT in OA-induced NAFLD rats increased about onefold and twofold ( p < 0.01), respectively, compared with the control group, indicating that rats fed with OA diet displayed severe NAFLD with liver injury. Those results were in agreement with our previous studies [ 4 , 34 ]. Figure 2.…”
Section: Resultssupporting
confidence: 94%
“…In another study, Liu et al . [ 4 ] also found EPA-PL from C. frondosas had protective effects against NAFLD [ 4 ]. However, SCS treatment for 10 days could only significantly reduce hepatic TC content, and the TG content was slightly decreased without remarkable difference.…”
Section: Resultsmentioning
confidence: 99%
“…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 ].…”
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.
“…Activities of AST and ALT in OA-induced NAFLD rats increased about onefold and twofold ( p < 0.01), respectively, compared with the control group, indicating that rats fed with OA diet displayed severe NAFLD with liver injury. Those results were in agreement with our previous studies [ 4 , 34 ]. Figure 2.…”
Section: Resultssupporting
confidence: 94%
“…In another study, Liu et al . [ 4 ] also found EPA-PL from C. frondosas had protective effects against NAFLD [ 4 ]. However, SCS treatment for 10 days could only significantly reduce hepatic TC content, and the TG content was slightly decreased without remarkable difference.…”
Section: Resultsmentioning
confidence: 99%
“…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 ].…”
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.
“…EPA‐enriched phosphatidylcholine (EPA‐PC) has been reported to mediate lipid metabolism, and it was therefore used as a reference in the present study. [ 14,15 ] The results of our study indicated that EPA‐PlsEtns significantly reduced serum and hepatic lipid levels via facilitating fatty acid β‐oxidation and by increasing cholesterol efflux and the synthesis of bile acids.…”
Decreased ethanolamine plasmalogen (PlsEtn) levels are observed in erythrocytes from patients with hyperlipidemia. Dietary PlsEtns can increase erythrocyte membrane PlsEtns and decrease plasma cholesterol; however, they do not affect triacylglycerol levels. In the present study, the effects of eicosapentaenoic acid-enriched PlsEtn (EPA-PlsEtn) on hyperlipidemia are evaluated in comparison to those of EPA-enriched phosphatidylcholine (EPA-PC) in senescence-accelerated mice (SAMP8). The results indicate that EPA-PlsEtn supplementation dramatically reduces triacylglycerol (42%, p < 0.01) and serum cholesterol (32%, p < 0.05) levels compared to those in the model group, while EPA-PC treatment does not significantly affect either of these parameters. Mechanistically, the triacylglycerol-lowering effect of EPA-PlsEtn may be attributed to accelerated fatty acid-oxidation that occurs due to the upregulation of carnitine palmitoyl transferase (CPT)-1a, CPT-2, and acyl-CoA oxidase 1 expression. Additionally, EPA-PlsEtn supplementation can reduce hepatic cholesterol levels via promoting cholesterol efflux mediated by ATP binding cassette subfamily G member 5 and the synthesis of bile acids regulated by farnesoid X receptor. These findings suggest that EPA-PlsEtn may be promising for use as a novel therapeutic agent for the treatment of age-related hyperlipidemia and metabolic disorder. Practical Applications: Supplementary EPA-PlsEtn can reduce both cholesterol and triacylglycerol levels in the serum and liver of SAMP8 mice, which contributes to the protection against age-related hyperlipidemia. EPA-PlsEtn supplementation accelerates hepatic fatty acid-oxidation and cholesterol efflux, which results in lowering serum lipid levels. EPA-PlsEtn and EPA-PC exert different effects on lipid metabolism via different metabolic pathways, which indicates the activity-structure relationship is worth further investigation.
“…Fish oils, mainly eicosapentaenoic acid (EPA) and docosahexanoic acid (DHA), represent one of the most highly marketed and widely used supplement types for many metabolic conditions [ 140 , 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 , 152 , 153 ]. They can improve lipid homeostasis and inflammation through the PPARα, AMPK, and adiponectin [ 140 , 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 , 152 , 153 ]. A 41-patient NASH study by Argo et al randomized patients to receive 3000 mg/day of fish oil or placebo for 1 year and observed improved ALT in the treated patients [ 140 ].…”
Our aim is to review the efficacy of various herbs and supplements as a possible therapeutic option in the treatment and/or prevention of nonalcoholic fatty liver disease (NAFLD). We performed a systematic review of medical literature using the PubMed Database by searching the chemical names of many common herbs and supplements with “AND (NAFLD or NASH)”. Studies and medical literature that discussed the roles and usage of herbs and supplements in NAFLD and nonalcoholic steatohepatitis (NASH) from inception until 20 June 2018 were reviewed. Many studies have claimed that the use of various herbs and supplements may improve disease endpoints and outcomes related to NAFLD and/or NASH. Improvement in liver function tests were noted. Amelioration or reduction of lobular inflammation, hepatic steatosis, and fibrosis were also noted. However, well-designed studies demonstrating improved clinical outcomes are lacking. Furthermore, experts remain concerned about the lack of regulation of herbs/supplements and the need for further research on potential adverse effects and herb–drug interactions. In conclusion, preliminary data on several herbs have demonstrated promising antioxidant, anti-inflammatory, anti-apoptotic, and anti-adipogenic properties that may help curtail the progression of NAFLD/NASH. Clinical trials testing the safety and efficacy must be completed before widespread use can be recommended.
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