Eicosapentaenoic acid (EPA) vs. Docosahexaenoic acid (DHA): Effects in epididymal white adipose tissue of mice fed a high-fructose diet. (August 2017) - Bargut, Thereza Cristina Lonzetti
Abstract: Background: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been demonstrated to be beneficial for many diseases, including those associated with the metabolic syndrome (e.g. insulin resistance and hypertension). Nevertheless, not only their actions are not entirely understood, but also their only effects were not yet elucidated. Therefore, we aimed to compare the effects of EPA and DHA, alone or in combination, on the epididymal white adipose tissue (WAT) metabolism in mice fed a high-fructose diet. Methods: 3-mo-old C57Bl/6 mice were fed a control diet (C) or a high-fructose diet (HFru). After three weeks on the diets, the HFru group was subdivided into four new groups for another five weeks: HFru, HFru+EPA, HFru+DHA, and HFru-EPA+DHA (n=10/group). Besides evaluating biometric and metabolic parameters of the animals, we measured the adipocyte area and performed molecular analyses (inflammation and lipolysis) in the epididymal WAT. Results: The HFru group showed adipocyte hypertrophy, inflammation, and uncontrolled lipolysis. The treated animals showed a reversion of adipocyte hypertrophy, inhibition of inflammation with activation of anti-inflammatory mediators, and regularization of lipolysis. Overall, the beneficial effects were more marked with DHA than EPA. Conclusion: Although the whole-body metabolic effects were similar between EPA and DHA, DHA appeared to be the central actor in WAT metabolism, modulating pro and anti-inflammatory pathways and alleviating adipocytes abnormalities. Therefore, when considering fructose-induced adverse effects in WAT, the most prominent actions were observed with DHA. Graphical abstract: EPA and DHA are beneficial to white adipose tissue of high-fructose fed mice, modulating inflammation by diminishing pro-inflammatory markers (dark purple) and increasing anti-inflammatory markers (light purple). The effects link with attenuation of genes involved in lipolysis (blue) and amelioration of AMPK and AKT phosphorylation (pink). DHA (green) has more noticeable effects than EPA (red) and affect all analyzed data. Highlights: EPA and DHA reversed metabolic alterations promoted by a high-fructose diet; In WAT, they decreased pro-inflammatory markers and increased anti-inflammatory ones; They also attenuated lipolysis of WAT and reduced insulin resistance; DHA showed stronger effects (alone or in combination with EPA) than EPA.