Fish Oil Feeding Decreases Mature Sterol Regulatory Element-binding Protein 1 (SREBP-1) by Down-regulation of SREBP-1c mRNA in Mouse Liver

Abstract

Dietary fish oil induces hepatic peroxisomal and microsomal fatty acid oxidation by peroxisome proliferator-activator receptor ␣ activation, whereas it downregulates lipogenic gene expression by unknown mechanism(s). Because sterol regulatory element-binding proteins (SREBPs) up-regulated lipogenic genes, investigation was made on the effects of fish oil feeding on SREBPs and sterol regulatory element (SRE)-dependent gene expression in C57BL/6J mice. Three forms of SREBPs, SREBP-1a, -1c, and -2, are expressed in liver, and their truncated mature forms activate transcription of sterol-regulated genes. C57BL/6J mice were divided into three groups; the first group was given a high carbohydrate diet, and the other two groups were given a high fat diet (60% of total energy), with the fat in the form of safflower oil or fish oil, for 5 months. Compared with safflower oil feeding, fish oil feeding decreased triglyceride and cholesterol concentrations in liver. There were no differences in amount of SREBP-1 and -2 in both precursor and mature forms between carbohydrate-and safflower oil-fed mice. However, compared with safflower oil feeding, fish oil feeding reduced the amounts of precursor SREBP-1 in membrane fraction by 90% and of mature SREBP-1 in liver nuclei by 57%. Fish oil feeding also reduced precursor SREBP-2 by 65% but did not alter the amount of mature SREBP-2. Compared with safflower oil feeding, fish oil feeding decreased liver SREBP-1c mRNA level by 86% but did not alter SERBP-1a mRNA. Consistent with decrease of mature SREBP-1, compared with safflower oil feeding, fish oil feeding down-regulated the expression of liver SRE-dependent genes, such as low density lipoprotein receptor, 3-hydroxy-3-methylglutaryl-CoA reductase, 3-hydroxy-3-methylglutaryl-CoA synthase, fatty acid synthase, acetyl-CoA carboxylase, and stearoyl-CoA desaturase-1. These data suggested that in liver, fish oil feeding downregulates the mature form of SREBP-1 by decreasing SREBP-1c mRNA expression, with corresponding decreases of mRNAs of cholesterologenic and lipogenic enzymes.

Effects of dietary lipids and Clostridium butyricum on serum lipids and lipid-related gene expression in broiler chickens

“…The mRNA level of SREBP-1c was not significantly influenced by lipid type or C. butyricum addition. This contradicts previous studies demonstrating that polyunsaturated fatty acids (PUFA) inhibited lipogenic gene transcription by suppressing SREBP-1c expression (Kim et al, 1999;Xu et al, 1999). Xu et al (1999) also indicated that the SREBP-1 mRNA content of cells was reduced by 20:4n-6 fatty acids in a dose-dependent manner, whereas 18:1n-9 had no effect.…”

“…There have been numerous reports on how fish oil affects fatty acid metabolism in mammals (Ribeiro et al, 1991;Kim et al, 1999;Yu et al, 2010), but few have focused on birds. Moreover, the effects of dietary C. butyricum on the expression of genes linked to fatty acid metabolism have not been examined in chickens.…”

Fish oil prevents sucrose-induced fatty liver but exacerbates high-safflower oil-induced fatty liver in ddy mice

“…Diet preparations were similar to those of our previous studies. 5,6 Fish oil was provided by NOF Corp. (Tokyo, Japan). Butter was purchased from Snow Brand Milk Corp. (Hokkaido, Japan).…”

“…4 This effect is attributable mainly to the combined effects of inhibition of lipogenesis and stimulation of fatty acid oxidation in the liver. 5,6 Fish oil supplementation may be effective in the prevention of NAFLD; however, it is not clear whether fish oil is effective against all types of fatty liver.…”

n-3 long chain polyunsaturated fatty acids: a nutritional tool to prevent insulin resistance associated to type 2 diabetes and obesity?

“…∆9 desaturase is regulated at the molecular level by SREBP-1c [63]. Kim et al [64] demonstrated that fish oil downregulated ∆9 desaturase expression by inhibiting the synthesis of mRNA of SREBP-1c. Thus, the inhibition of ∆9 desaturase is with its inhibiting effect on lipogenesis and its stimulating effect on fatty acid oxidation another mechanism by which it decreases lipid synthesis and triglycerides in the liver.…”