Abstract
Diets containing various docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA) ratios protect against liver damage in mice fed with a high-fat diet (HFD). However, it is unclear whether these beneficial roles of DHA and EPA are associated with alterations of fatty acid (FA) composition in the liver. This study evaluated the positive impacts of n-6/n-3 polyunsaturated fatty acids (PUFAs) containing different DHA/EPA ratios on HFD-induced liver disease and alterations of the hepatic FA composition. ApoE−/− mice were fed with HFDs with various ratios of DHA/EPA (2 : 1, 1 : 1, and 1 : 2) and an n-6/n-3 ratio of 4 : 1 for 12 weeks. After treatment, the serum and hepatic FA compositions, serum biochemical parameters, liver injury, and hepatic lipid metabolism-related gene expression were determined. Our results demonstrated that dietary DHA/EPA changed serum and hepatic FA composition by increasing contents of n-6 and n-3 PUFAs and decreasing amounts of monounsaturated fatty acids (MUFAs) and the n-6/n-3 ratio. Among the three DHA/EPA groups, the DHA/EPA 2 : 1 group tended to raise n-3 PUFAs concentration and lower the n-6/n-3 ratio in the liver, whereas DHA/EPA 1 : 2 tended to raise n-6 PUFAs concentration and improve the n-6/n-3 ratio. DHA/EPA supplementation reduced the hepatic impairment of lipid homeostasis, oxidative stress, and the inflammatory responses in HFD-fed mice. The DHA/EPA 2 : 1 group had lower serum levels of total cholesterol, triglycerides, and low-density lipoprotein cholesterol and higher levels of adiponectin than HFD group. The DHA/EPA 1 : 2 group had elevated serum levels of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase, without significant change the expression of genes for inflammation or hepatic lipid metabolism among the three DHA/EPA groups. The results suggest that DHA/EPA-enriched diet with an n-6/n-3 ratio of 4 : 1 may reverse HFD-induced nonalcoholic fatty liver disease to some extent by increasing n-6 and n-3 PUFAs and decreasing the amount of MUFAs and the n-6/n-3 ratio.
Highlights
Nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease worldwide, is one of the major causes of the fatty liver, occurring when fat is deposited in the liver in the absence of excessive alcohol intake [1, 2]
We previously showed that an oral administration of n-6/n-3 polyunsaturated fatty acids (PUFAs) with varying docosahexaenoic acid (DHA)/EPA ratios for 12 weeks ameliorated atherosclerosis lesions [24] and liver damage [17] in mice fed with an high-fat diet (HFD)
Among the varying ratios of DHA/EPA groups, we found an increase in saturated fatty acids (SFAs) (DHA/EPA 2 : 1 group, 19.6%; DHA/ EPA 1 : 1 group, 14.5%), PUFAs n-6 series (DHA/EPA 2 : 1 group, 11.1%; DHA/EPA 1 : 1 group, 9.1%; and DHA/EPA 1 : 2 group, 17.9%), and PUFA n-3 series (DHA/EPA 2 : 1 group, 166.4%; DHA/EPA 1 : 1 group, 151.7%; and DHA/ EPA 1 : 2 group, 126.3%) in the liver compared to the HFD group
Summary
Nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease worldwide, is one of the major causes of the fatty liver, occurring when fat is deposited in the liver in the absence of excessive alcohol intake [1, 2]. Lifestyle modification, including dietary changes, weight loss, and physical activity, is the initial treatment option for patients with NAFLD [8]. Dietary modification may benefit the treatment of NAFLD without significant weight loss [9]. Jump et al [14] provided an in-depth rationale for the use of dietary n-3 PUFA supplements as a treatment option for NAFLD. Experimental and clinical data on n-3 PUFAs have demonstrated that dietary supplementation with eicosapentaenoic acid (EPA, C20:5) and docosahexaenoic acid (DHA, C22:6) prevents or alleviates NAFLD [15]. We reported that diet rich in DHA and/or EPA improved lipid metabolism and had antiinflammatory effects in HFD-induced NALFD in C57BL/6J mice [17]. The precise requirement for marine n-3 PUFAs is not known [9]
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