Abstract
BackgroundNonalcoholic fatty liver disease is the most common chronic liver disease in the world, and is becoming increasingly prevalent. Saponins of sea cucumber (SSC) are proven to exhibit various biological activities. Therefore, the present study was undertaken to examine the effect of saponins extracted from sea cucumber (Pearsonothuria graeffei) on the preventive activity of fatty liver in rats.MethodsMale Wistar rats were randomly divided into five groups, including normal control group, fatty liver model group, SSC-treated group with SSC at levels of 0.01%, 0.03% and 0.05%. Model rats were established by administration with 1% orotic acid (OA). After the experiment period, serum total cholesterol (TC), triglyceride (TG), and hepatic lipid concentrations were determined. To search for a possible mechanism, we examined the changes of key enzymes and transcriptional factors involved in hepatic lipids biosynthesis, fatty acid β-oxidation.ResultsBoth 0.03% and 0.05% SSC treatment alleviated hepatic steatosis and reduced serum TG and TC concentration significantly in OA fed rats. Hepatic lipogenic enzymes, such as fatty acid synthase (FAS), malic enzyme (ME), and glucose-6-phosphate dehydrogenase (G6PDH) activities were inhibited by SSC treatment. SSC also decreased the gene expression of FAS, ME, G6PDH and sterol-regulatory element binding protein (SREBP-1c). Otherwise, the rats feeding with SSC showed increased carnitine palmitoyl transferase (CPT) activity in the liver. Hepatic peroxisome proliferator-activated receptor (PPARα), together with its target gene CPT and acyl-CoA oxidase (ACO) mRNA expression were also upregulated by SSC.ConclusionsAccording to our study, the lipids-lowering effect of dietary SSC may be partly associated with the enhancement of β-oxidation via PPARα activation. In addition, the inhibited SREBP-1c- mediated lipogenesis caused by SSC may also contribute to alleviating fatty liver.
Highlights
Nonalcoholic fatty liver disease is the most common chronic liver disease in the world, and is becoming increasingly prevalent
Hepatic enzyme activities involved in lipids biosynthesis We examined the activities of critical enzymes in the liver involved in lipids biosynthesis, including fatty acid synthase (FAS), malic enzyme (ME) and glucose-6-phosphate dehydrogenase (G6PDH)
Relative mRNA concentrations of sterolregulatory element binding protein (SREBP)-1c and its target genesin the liver To explore the molecular mechanism by which Saponins of sea cucumber (SSC) may regulate the different transcription factors and enzymes related in lipids metabolism, we examined the expression of hepatic genes that regulate lipogenesis. 1% orotic acid (OA) administration markedly increased the expression of hepatic SREBP-1c mRNA (P < 0.01) and the target lipogenic gene
Summary
Nonalcoholic fatty liver disease is the most common chronic liver disease in the world, and is becoming increasingly prevalent. Saponin ( called triterpene glycoside), is the most important secondary metabolite and bioactive composition of sea cucumber, which has been proven to exhibit various biological activities, such as including antifungal, anti-angiogenesis, anti-tumor and immunomodulatory effects [11,12,13]. It is unknown whether saponins of sea cucumber (SSC) may improve lipid metabolism in animal models. Several lines of evidence indicate that orotic acid (OA) administration induces fatty liver [14,15]
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