Author : Dawn Fedor
Publisher :
ISBN 13 : 9781303442483
Total Pages : pages
Book Rating : 4.4/5 (424 download)
Book Synopsis Prevention of CLA-induced Insulin Resistance and Nonalcoholic Fatty Liver Disease by Docosahexaenoic Acid in Mice by : Dawn Fedor
Download or read book Prevention of CLA-induced Insulin Resistance and Nonalcoholic Fatty Liver Disease by Docosahexaenoic Acid in Mice written by Dawn Fedor and published by . This book was released on 2013 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Insulin resistance (IR) is a condition in which normal amounts of insulin fail to maintain normal blood glucose because of decreased responsiveness of muscle (glucose uptake), liver (inhibition of gluconeogenesis) and adipocytes (inhibition of lipolysis). IR is often associated with nonalcoholic fatty liver disease (NAFLD), the most common liver disease in adults and children in the Western world. Results from human epidemiological studies indicate that n-3 PUFA reduce the development of IR and NAFLD although the mechanisms involved are poorly understood. Our lab previously showed that concomitant supplementation of 1.5% docosahexaenoic acid (22:6 n-3; DHA) with 0.5% t10, c12- conjugated linoleic acid (18:2 n-6; CLA) prevented the CLA-induced NAFLD and IR. The effective dose of DHA, the mechanisms involved and the effect of CLA on fatty acid compositions of adipose tissue and muscle, and whether DHA can prevent those CLA-induced changes in fatty acid composition is not known. In the first study, we examined the ability of DHA (0.5 and 1.5%) to prevent increases in NAFLD and homeostatic model assessment of insulin resistance (HOMA-IR) induced by CLA (0.5%) when fed concomitantly for 4 weeks to C57BL/6N female mice. We also examined changes in expression of hepatic genes involved in fatty acid synthesis and oxidation. CLA supplementation increased liver triglycerides (TG) and HOMA-IR by 221 and 547%, respectively, and decreased mass of adipose depots by 65-90%. When fed concomitantly, 0.5% and 1.5% DHA prevented CLA-induced increases in liver TG and circulating insulin with varying efficiency, but neither dose of DHA prevented the loss in adipose tissue mass. In CLA + DHA 0.5 % group the liver TG did not differ from those in the control group, but circulating insulin and HOMA-IR were 285 and 264 %, respectively, greater than those in the control group. In the CLA + DHA 1.5% group liver TG were 54% lower than those in the control group, but circulating insulin concentration and HOMA-IR did not differ between these two groups. CLA increased the expression of hepatic genes involved in fatty acid synthesis and decreased the expression of genes involved in fatty acid oxidation. 1.5% DHA prevented changes in the expression of hepatic genes caused by CLA, which may be a possible mechanism contributing to the prevention of TG accumulating in the liver. Based on these results, we further studied the 1.5% DHA diet. We investigated the effects of 1.5% DHA concomitantly fed with CLA on fatty acid compositions of liver, adipose, and muscle lipids in the same mice, as well as expression of genes involved in adipose fatty acid metabolism. CLA supplementation decreased total hepatic n-3 PUFA concentration. DHA not only prevented the CLA-induced changes in liver fat, but also increased n-3 PUFA by >350% as compared with the control group. CLA decreased adipose weight and the expression of genes involved in fatty acid synthesis, oxidation, and uptake, and increased that of UCP2 in the adipose. Supplementing DHA along with CLA increased adipose n-3 PUFA by >1000% compared with control group, but did not prevent the CLA-induced changes in mass or gene expression. Both CLA and DHA were incorporated into muscle lipids, but had minor effects on FA composition. In conclusion, liver, adipose tissue, and muscle responded differently to CLA and DHA supplementation. CLA was more potent than DHA in altering depot fat and insulin concentration. DHA prevented CLA-induced increase in liver fat but not loss of adipose mass. CLA and DHA were preferentially incorporated into adipose tissue lipids, but they had only modest effects on the overall fatty acid composition of the adipose tissue. The largest changes in fatty acid composition were seen in the liver and smallest in muscle lipids.