Submitted to: American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/8/2013
Publication Date: 3/26/2014
Citation: Wang, S., Matthan, N.R., Wu, D., Reed, D.B., Bapat, P., Yin, X., Grammas, P., Shen, C., Lichtenstein, A.H. 2014. Lipid content in hepatic and gonadal adipose tissue parallel aortic cholesterol accumulation in mice fed diets with different omega-6 PUFA to EPA plus DHA ratios. American Journal of Clinical Nutrition. 33:260-266. Interpretive Summary: Diets high in fish are associated with lower risk of atherosclerosis. This effect is thought to be mediated by fatty acids unique to fish, referred to as omega-3 polyunsaturated fatty acids (PUFAs), particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Less well understood is the mechanism responsible for their role in reducing heart disease risk. Some data suggests that omega-3 fatty acids may have effects on liver and fat tissue and these effects contribute to heart health. LDL receptor null mice, mice that develop atherosclerosis, were used to assess the effect of a heart unhealthy diet containing different amounts of EPA+DHA on weight gain, liver and fat tissue fat accumulation, and their relationship to aortic cholesterol content. Four groups of mice were fed a high saturated fat and cholesterol diet alone, or with increasing amounts of omega EPA and DHA. The higher the level of EPA and DHA in the diet, the higher these fatty acids were in the liver and fat tissue. All diets resulted in similar weight gains. The diets with the highest level of EPA and DHA resulted in lower liver cholesterol content. Aortic total cholesterol was positively correlated with liver and fat tissue cholesterol and triglyceride content. These differences were accompanied by significantly lower expression of genes involved in cholesterol homeostasis. The lower accumulation of liver cholesterol may be related to the lower aortic cholesterol accumulation.
Technical Abstract: Diets with low omega (u)-6 polyunsaturated fatty acids (PUFA) to eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) ratios have been shown to decrease aortic cholesterol accumulation and have been suggested to promote weight loss. The involvement of the liver and gonadal adipose tissue (GAT) in mediating these effects is not well understood. LDL receptor null mice were used to assess the effect of an atherogenic diet with different u-6:EPA+DHA ratios on weight gain, hepatic and GAT lipid accumulation, and their relationship to atherosclerosis. Four groups of mice were fed a high saturated fat and cholesterol diet (HSF u-6) alone, or with u-6 PUFA to EPAþDHA ratios up to 1:1 for 32 weeks. Liver and GAT were collected for lipid and gene expression analysis. The fatty acid profile of liver and GAT reflected the diets. All diets resulted in similar weight gains. Compared to HSF u-6 diet, the 1:1 ratio diet resulted in lower hepatic total cholesterol (TC) content. Aortic TC was positively correlated with hepatic and GAT TC and triglyceride. These differences were accompanied by significantly lower expression of CD36, ATP-transporter cassette A1, scavenger receptor B class 1, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), acetyl-CoA carboxylase alpha, acyl-CoA synthetase long-chain family member 5, and stearoyl-coenzyme A desaturase 1 (SCD1) in GAT, and HMGCR, SCD1 and cytochrome P450 7A1 in liver. Dietary u-6:EPA+DHA ratios did not affect body weight, but lower u-6:EPA+DHA ratio diets decreased liver lipid accumulation, which possibly contributed to the lower aortic cholesterol accumulation.