Docosahexaenoic acid suppresses the expression of FoxO and its target genes
Journal
Journal of Nutritional Biochemistry
Journal Volume
23
Journal Issue
12
Pages
1609-1616
Date Issued
2012
Author(s)
Chen Y.-J.
Chen C.-C.
Wang P.-H.
Liu L.-R.
Chang F.-Y.
Wang Y.-C.
Yu Y.-H.
Lin S.-P.
Mersmann H.J.
Abstract
Docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid, has previously been shown to ameliorate obesity-associated metabolic syndrome. To decipher the mechanism responsible for the beneficial effects of DHA on energy/glucose homeostasis and the metabolic syndrome, 30 weaned cross-bred pigs were randomly assigned to three groups and fed ad libitum with a standard diet supplemented with 2% of beef tallow, soybean oil or DHA oil for 30 days, and the gene expression profile of various tissues was evaluated by quantitative real-time polymerase chain reaction. The DHA-supplemented diets reduced the expression of forkhead box O transcription factor (FoxO) 1 and FoxO3 in the liver and adipose tissue. DHA treatments also decreased the expression of FoxO1 and FoxO3 in human hepatoma cells, SK-HEP-1 and human and porcine primary adipocytes. In addition, DHA also down-regulated FoxO target genes, such as microsomal triacylglycerol transfer protein (MTP), glucose-6-phosphatase, apolipoprotein C-III (apoC-III) and insulin-like growth factor binding-protein 1 in the liver, as well as reduced total plasma levels of cholesterol and triacylglycerol in the pig. Transcriptional suppression of FoxO1, FoxO3, apoC-III and MTP by DHA was further confirmed by reporter assays with each promoter construct. Taken together, our study indicates that DHA modulates lipid and glucose homeostasis in part by down-regulating FoxO function. The down-regulation of genes associated with triacylglycerol metabolism and very low density lipoprotein assembly is likely to contribute to the beneficial effects of DHA on the metabolic syndrome. ? 2012.
SDGs
Other Subjects
apolipoprotein C3; cholesterol; docosahexaenoic acid; glucose 6 phosphatase; microsomal triglyceride transfer protein; somatomedin binding protein 1; soybean oil; transcription factor FKHR; transcription factor FKHRL1; triacylglycerol; adipocyte; adipose tissue; animal cell; animal experiment; animal tissue; article; beef; cholesterol blood level; controlled study; diet supplementation; down regulation; experimental pig; female; gene expression; gene targeting; gluconeogenesis; glucose homeostasis; hepatoma cell; human; human cell; lipid metabolism; liver; male; nonhuman; nucleotide sequence; promoter region; real time polymerase chain reaction; triacylglycerol blood level; Adipocytes; Adipose Tissue; Animals; Carcinoma, Hepatocellular; Cell Line, Tumor; Cholesterol; Dietary Supplements; Docosahexaenoic Acids; Female; Forkhead Transcription Factors; Gene Expression Regulation; Glucose; Humans; Lipid Metabolism; Liver; Liver Neoplasms; Male; Real-Time Polymerase Chain Reaction; Swine; Triglycerides; Glycine max; Suidae; Sus
Type
journal article