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ARS Home » Pacific West Area » Davis, California » Western Human Nutrition Research Center » Immunity and Disease Prevention Research » Research » Publications at this Location » Publication #273422
Title: Docosahexaenoic acid prevents trans-10, cis-12 conjugated linoleic acid-induced non-alcoholic fatty liver disease in mice by altering expression of hepatic genes regulating fatty acid synthesis and oxidation

Author
item Fedor, Dawn
item Adkins, Yuriko
item Mackey, Bruce
item Kelley, Darshan

Submitted to: Metabolic Syndrome and Disorders
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/1/2011
Publication Date: 6/1/2012
Citation: Fedor, D.M., Adkins, Y.C., Mackey, B.E., Kelley, D.S. 2012. Docosahexaenoic acid prevents trans-10, cis-12 conjugated linoleic acid-induced non-alcoholic fatty liver disease in mice by altering expression of hepatic genes regulating fatty acid synthesis and oxidation. Metabolic Syndrome and Disorders. 10(3):175-180. DOI: 10.1089/met.2011.0113.

Interpretive Summary: Non-alcoholic fatty liver disease (NAFLD) develops when fatty acid uptake and synthesis in the liver exceeds oxidation and export as triglycerides (TG). It is the number one liver disease in the Western world and if not treated it leads to liver failure. It is often associated with obesity, insulin resistance (IR) and type 2 diabetes. Consumption of diets high in fat, particularly the saturated and trans fatty acids, increases the incidence of NAFLD and IR, while consumption of diets high in omega-3 fatty acids decreases the incidence of these metabolic disorders. Conjugated linoleic acid (t10, c12-CLA) is one of the major trans fatty acids found in processed foods and partially hydrogenated vegetable oils; it has been found to cause IR and NAFLD in animal models. We previously reported that docosahexaenoic acid (DHA), one of the long chain omega-3 polyunsaturated fatty acids found in fish oils, prevented the CLA-induced NAFLD and IR in the mouse model. Effective dose of DHA needed to prevent the adverse effects of CLA, and the mechanisms involved are not known. We tested the ability of DHA (0.5 and 1.5%) to prevent NAFLD and 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. In these studies, CLA supplementation increased liver TG and circulating insulin by 257% and 500% and decreased mass of different adipose depots by 65-90%. When fed concomitantly, DHA prevented CLA-induced increases in liver TG and circulating insulin with varying efficiency, but it did not prevent loss in adipose tissue mass. In CLA + DHA 0.5% group circulating insulin was 285% greater than those in control group, but liver TG was restored to the level found in the control group. In CLA + DHA 1.5% group circulating insulin was restored to the level found in the control group, but liver TG were decreased by 54% as compared to those found in the control group. CLA increased expression of hepatic genes involved in fatty acid synthesis and decreased those of genes involved in fatty acid oxidation. DHA 1.5% prevented changes in the expression of hepatic genes caused by CLA. Our results suggest that an increase in the consumption of omeg-3 polyunsaturated fatty acids may prevent IR and NAFLD by trans fatty acids.

Technical Abstract: Background: Concomitant supplementation with docosahexaenoic acid (22:6 n-3; DHA) prevented t10, c12- conjugated linoleic acid (CLA)-induced non-alcoholic fatty liver disease (NAFLD) and insulin resistance. Effective dose of DHA and mechanisms involved are poorly understood. Methods: We examined 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. Results: CLA supplementation increased liver triglycerides (TG) and HOMA-IR by 257 and 500% and decreased mass of adipose depots by 65-90%. When fed concomitantly, DHA prevented CLA-induced increases in liver TG and circulating insulin with varying efficiency, but it did not prevent loss in adipose tissue mass. In CLA + DHA 0.5% group liver TG did not differ from those in control group, but circulating insulin and HOMA-IR were 285% greater than those in control group. In CLA + DHA 1.5% group liver TG were 54% lower than those in control group, but circulating insulin concentration and HOMA-IR did not differ between these two groups. CLA increased expression of hepatic genes involved in fatty acid synthesis and decreased expression of genes involved in fatty acid oxidation. DHA 1.5% prevented changes in the expression of hepatic genes caused by CLA. Conclusions: Response of different tissues to CLA and DHA varied; CLA was more potent than DHA in altering depot fat and insulin concentration.