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United States Department of Agriculture

Agricultural Research Service

Title: Docosahexaenoic Acid (DHA) But Not Eicosapentaenoic Acid (EPA) Reverses Trans-10, Cis-12 Conjugated Linoleic Acid Induced Insulin Resistance in Mice1

Authors
item Vemuri, Madhuri - UCD NUTR. DEPT./WHNRC
item Kelley, Darshan
item Mackey, Bruce
item Rasooly, Reuven
item Bartolini, Giovanni

Submitted to: Trade Journal Publication
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: October 1, 2007
Publication Date: December 1, 2007
Citation: Vemuri, M., Kelley, D.S., Mackey, B.E., Rasooly, R., Bartolini, G.L. Docosahexaenoic Acid (DHA) But Not Eicosapentaenoic Acid (EPA) Reverses Trans-10, Cis-12 Conjugated Linoleic Acid Induced Insulin Resistance in Mice. Metabolic Syndrome and Related Disorders, 2007 Vol.5, No.4:315-322.

Interpretive Summary: One type of conjugated linoleic acid (t10, c12-CLA) that is found in partially hydrogenated vegetable oils has been found to cause insulin resistance and fatty liver in animal models including mice. Concomitant supplementation with fish oils has been found to reverse the CLA-induced insulin resistance and fatty liver. Fish oils are the sources of two major n-3 fatty acids, eicosapentaenoic acid (20:5n-3, EPA) and docosahexaenoic acid (22:6n-3, DHA). It is not known if it is the EPA or DHA in fish oils that reverses these adverse effects of CLA. In this study conducted at the Western Human Nutrition Research Center, eight-week-old, pathogen-free C57BL/6N female mice (10 per group) were fed either a control diet or diets containing t10, c12-CLA (0.5 wt %) or CLA +DHA (0.5% + 1.5 wt %), or CLA + EPA (0.5% + 1.5 wt %) for 8 weeks prior to sacrifice and tissue collection. CLA supplementation caused a greater than four fold increase in circulating insulin, a 2.6 fold increase in liver weights and a greater than 6 fold increase in the weight of mean total lipids in livers as compared with the corresponding values in the control group. DHA reversed the CLA induced insulin resistance, while EPA was completely ineffective. Both EPA and DHA reversed CLA induced fatty liver and reduced weights of total liver lipids to the levels in the control group. CLA also reduced the plasma leptin and adiponectin concentrations to approximately 15% of those in the control group. Both EPA and DHA partially restored the CLA-induced decrease in leptin, but only DHA partially restored the plasma adiponectin. Our results suggest that only the DHA and not EPA in fish oils may reduce insulin resistance, while both these fatty acids can reverse the development of fatty liver. These finding may have significant impact in the prevention and management of diabetes and fatty liver in humans if the effects of DHA in humans are similar to those in mice.

Technical Abstract: Objective: t10, c12-Conjugated linoleic acid (CLA) induces insulin resistance and fatty liver in mice which can be reversed by fish oils. We determined if it is eicospentaenoic acid (20:5n-3, EPA) or docoshexaenoic acid (22:6n-3, DHA) that reverses these adverse effects of CLA. Research Design and Methods: Eight-week-old, pathogen-free C57BL/6N female mice (10 per group) were fed either a control diet or diets containing t10, c12-CLA (0.5 wt %) or CLA +DHA (0.5% + 1.5 wt %), or CLA + EPA (0.5% + 1.5 wt %) for 8 weeks prior to sacrifice and tissue collection. Results: CLA supplementation caused a greater than four fold increase in circulating insulin, a 2.6 fold increase in liver weights and a greater than 6 fold increase in the weight of total lipids in liver as compared with the corresponding values in the control group. DHA reversed the CLA induced insulin resistance, while EPA was completely ineffective. Both EPA and DHA reversed CLA induced fatty liver and reduced weights of total liver lipids to the levels in the control group. CLA also reduced the plasma leptin and adiponectin concentrations to approximately 15% of those in the control group. Both EPA and DHA partially restored the CLA-induced decrease in leptin, but only DHA partially restored the plasma adiponectin. Conclusion: Our results suggest that only the DHA and not EPA in fish oils may reduce insulin resistance. These findings may have clinical implications. Conjugated linoleic acid (CLA) refers to linoleic acid isomers having conjugated double bonds. The two isomers that have been most commonly studied are c9, t11-CLA and t10, c12-CLA. Dairy products and ruminant meats are the major sources of c9, t11-CLA, while t10, c12-CLA is found primarily in partially hydrogenated vegetable oils (1). Supplementing human as well as animal diets with CLA has been claimed to decrease body fat and also reduce the incidences of diabetes, atherosclerosis and cancer (2-4), and references therein). Though health benefits of CLA have not been well established, adverse effects like increased insulin resistance and fatty liver after CLA supplementation is well documented in several animal models (5-10). Several studies have shown that t10, c12-CLA and not c9, t11-CLA is the isomer that causes fatty liver and insulin resistance and (2-4). N-3 polyunsaturated fatty acids (PUFA) from fish oils have been shown to reverse insulin resistance induced by high fat (11; 12) or high sucrose (13) diets or by diets containing CLA (14; 15). Fish oils have also been shown to reduce CLA induced fatty liver (14). However, diets supplemented with docosahexaenoic acid (22:6n-3, DHA), one of the abundant fatty acids in fish oils, failed to reverse CLA induced insulin resistance in mice (16). Role of each of the two major n-3 fatty acids, eicospentanoic acid (20:5n-3, EPA) and DHA in the prevention of fatty liver and insulin resistance have not been studied. In the present study, we investigated if purified DHA, EPA or both can reverse t10, c12-CLA induced fatty liver and insulin resistance. We also examined plasma concentrations of lipids, leptin and adiponectin because of their role in affecting insulin resistance and sensitivity.

Last Modified: 11/21/2014
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