Dietary DHA/EPA Ratio Changes Fatty Acid Composition and Attenuates Diet‐Induced Accumulation of Lipid in the Liver of ApoE^−/− Mice

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.

Effects of Long-Term DHA Supplementation and Physical Exercise on Non-Alcoholic Fatty Liver Development in Obese Aged Female Mice

“…Thus, increasing AMPK activities has been considered as a therapeutic approach to improve NAFLD [124]. Although several studies conducted in younger mice models of NAFLD have illustrated that short-or medium-term n-3 PUFA supplementation [27,82,94,125,126], and exercise interventions [37,39,106,111,127,128] can increase AMPK activation, to our knowledge our study is the first addressing the combined effects of long-term n-3 PUFA supplementation and exercise training on AMPK activation in obese aged mice.…”

Novel high‐docosahexaenoic‐acid tuna oil supplementation modulates gut microbiota and alleviates obesity in high‐fat diet mice

“…However, the fish oils used in these studies were commercially available fish oil with a higher EPA content (Molinar-Toribio et al, 2015;Parker et al, 2019). Additional evidence has indicated the role of the ratios of DHA and EPA in the prevention and treatment of chronic disease in rat models (Liu et al, 2018;Molinar-Toribio et al, 2015). Furthermore, a study (Cottin et al, 2011) explored the known differential effects of EPA and DHA in human subjects and concluded that there is an F I G U R E 5 Changes in the gut microbiota related to HDTO and TO supplementation.…”

DHA Supplementation Attenuates MI-Induced LV Matrix Remodeling and Dysfunction in Mice

“…The present study used diets with similar omega-6 FA content and higher preformed DHA, but not EPA in DHA diet, in order to decrease confounding by individual and rate-limiting differences in long-chain polyunsaturated fatty acid metabolism [41]. Furthermore, the herein used concentration has been shown to increase DHA serum and tissue concentrations [31,42], which was beneficial in pulmonary and neurological diseases in rodents [32,33]. Male mice were chosen to eliminate the complex cardioprotective effects that have been reported for all estrogen receptor subtypes against I/R injury, and a purified diet was chosen as the basis for both diets to avoid variability in standard chows [43].…”