Effects of Eicosapentaenoic Acid Supplementation in obese Transgenic Mouse Model of Alzheimer's Disease. (20th December 2022)

• Record Type: Journal Article
• Authors: Razafimanjato, Fitia; Yavari, Mahsa; Chavira, Angela; Davis, Mckenna; Ramalingam, Latha; Harris, Breanna N.; Zu, Yujiao; Moustaid‐Moussa, Naima
• Is Part Of: Alzheimer's & dementia. Volume 18(2022)Supplement 3
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-12-20
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.068334
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: Alzheimer'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. Method: Wild‐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. Result: Overall, 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). Conclusion: Our 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.