Regulation of Forkhead Box O Transcription Factors by Docosahexaenoic Acid
Date Issued
2009
Date
2009
Author(s)
Chen, Yu-Jen
Abstract
Obesity is closely linked to insulin resistance or type 2 diabetes mellitus. Obesity is also associated with hypertension, atheroschlerosis, glucose intolerance, dyslipidemia, and chronic inflammation, also known as the metabolic syndrome. Docosahexaenoic acid (DHA) is one of the n-3 polyunsaturated fatty acids and USA FDA had announced on 2004 that DHA and EPA could reduce the risk of coronary heart disease in conventional foods.o decipher beneficial effects of DHA on lipid and glucose metabolism, thirty weaned pigs were divided into three groups and fed ad librium for thirty days with a diet plus either 2% tallow, soybean or DHA oil, respectively. At the end of experiment, pigs were sedated and killed by electrical stunning. Viscera and blood samples were collected. Tissues were homogenized and total RNA was extracted for mRNA determination. Primers were designed for screening several genes involved in lipid metabolism and chronic inflammatory markers which may be regulated by supplementation of DHA oil. Supplementation of DHA on pig diets didn’t influence the expression of anti- or pro-infiltration cytokines, including interleukin 4 (IL4), IL6, IL10, IL13 and Tumor necrosis factor α (TNFα) in adipose tissues. Herein, we demonstrated a new transcription factor which DHA regulates. The class O of forkhead box transcription factors (FoxO) including FoxO1 and FoxO3 were decreased in the liver and adipose tissues of DHA-supplemented pigs compared with tallow-supplemented pigs. Pig diets containing DHA also decreased the cofactor of FoxO, PPARγ coactivator-1α (PGC1α), expression in both liver and adipose tissues. Similar results could also be found in human and pig primary adipocytes treated with DHA for 24 hours. Pigs fed with diets supplemented with DHA also down-regulated FoxO-target genes such as microsomal triglyceride transfer protein (MTTP), a protein which is involved in hepatic VLDL assembly. Expression of Glucose-6-phosphatase (G6Pase) participated in gluconeogenesis, apolipoprotein CⅢ (apoCⅢ) involved in TG secretion and insulin-like growth factor binding protein 1 (IGFBP1) was also reduced. Pigs supplemented with DHA also reduced plasma total cholesterol and triglyceride concentrations. n conclusion, DHA may partially act through down-regulation of FoxO function to influence lipid and glucose metabolism. Down-regulation of genes related triglyceride metabolism and VLDL assemble may implicate the prevention and beneficial role of DHA on metabolic syndrome.
Subjects
Weaned pigDHA
FoxO
metabolic syndrome
SDGs
Type
thesis
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