Brown adipose tissue (BAT) plays a key role in energy expenditure through its specialized thermogenic function. Therefore, BAT activation may help prevent and/or treat obesity. Interestingly, subcutaneous white adipose tissue (WAT) also has the ability to differentiate into brown-like adipocytes and may potentially contribute to increased thermogenesis. We have previously reported that eicosapentaenoic acid (EPA) reduces high-fat (HF)-diet-induced obesity and insulin resistance in mice. Whether BAT mediates some of these beneficial effects of EPA has not been determined. We hypothesized that EPA activates BAT thermogenic program, contributing to its antiobesity effects. BAT and WAT were harvested from B6 male mice fed HF diets supplemented with or without EPA. HIB 1B clonal brown adipocytes treated with or without EPA were also used. Gene and protein expressions were measured in adipose tissues and H1B 1B cells by quantitative polymerase chain reaction and immunoblotting, respectively. Our results show that BAT from EPA-supplemented mice expressed significantly higher levels of thermogenic genes such as PRDM16 and PGC1α and higher levels of uncoupling protein 1 compared to HF-fed mice. By contrast, both WATs (subcutaneous and visceral) had undetectable levels of these markers with no up regulation by EPA. HIB 1B cells treated with EPA showed significantly higher mRNA expression of PGC1α and SIRT2. EPA treatment significantly increased maximum oxidative and peak glycolytic metabolism in H1B 1B cells. Our results demonstrate a novel and promising role for EPA in preventing obesity via activation of BAT, adding to its known beneficial anti-inflammatory effects.

BackgroundAlzheimer’s disease (AD) is a progressive brain disease characterised by cerebral aggregation of amyloid beta (Aβ) plaques. Obesity is a chronic complex disease characterised by excessive fat accumulation, that is associated with systemic and adipose tissue inflammation, and may increase the risk for AD. Eicosapentaenoic acid (EPA) found in fish oil, is an omega‐3 polyunsaturated fatty acid with anti‐obesity and anti‐inflammatory properties. In this study, we propose that EPA supplementation will protect against AD‐associated metabolic dysfunctions in diet‐induced obese mice. We aim to determine the mechanisms mediating EPA effects in obesity‐related metabolic impairments in diet‐induced obese APPswePS1dE9 AD mouse model.MethodWild‐type (WT) and transgenic Alzheimer’s (TG) male and female mice were randomly assigned to either a low‐fat LF (10% kcal fat), a high‐fat (HF, 45% kcal fat), or a HF diet supplemented with 36 g/kg EPA (EPA) for 8 months. Body weights were measured weekly and tissues including adipose tissue were collected at the end of the intervention for analyses of genes involved in inflammation (TNF, fatty acid synthesis (ACACA), fatty acid oxidation (CPT1). Data were analysed by three‐way ANOVA using GraphPad Prism.ResultOverall, TG females gained less weight in HF and EPA groups, compared to male mice (P = 0.0075 and P < 0.0001, respectively). Moreover, TNF was lower in EPA groups compared to HF groups. Significant main effects were observed for sex in TNF, ACACA, and CPT1 (P<0.0001, P=0.0008, and P<0.0001, respectively). Main effects for genotype were observed for ACACA and CPT1 expression (P=0.0497 and P=0.0318, respectively). Main effects for diet (LF vs HF) were observed for TNF, ACACA, and CPT1 (P=<0.0001, P=0.0004, and P=0.0040, respectively). Moreover, significant main effects of HF vs EPA were observed for ACACA (P=0.0497). Interactions in sex x diet (LF vs HF and HF vs EPA) were observed for TNF (P=0.0003 and P=0.0252, respectively), also in sex x diet (LF vs HF) interactions for CPT1 (P=0.0086).ConclusionOur findings showed that EPA counteracted both inflammation and obesity induced by HF diets, especially in female mice. Further analyses are ongoing to determine mechanisms underlying potential benefits of EPA in obesity‐associated AD.

No abstract