| First Author | Yavari M | Year | 2023 |
| Journal | J Nutr | Volume | 153 |
| Issue | 4 | Pages | 1038-1051 |
| PubMed ID | 36781072 | Mgi Jnum | J:368499 |
| Mgi Id | MGI:8215278 | Doi | 10.1016/j.tjnut.2023.01.030 |
| Citation | Yavari M, et al. (2023) Eicosapentaenoic Acid Protects against Metabolic Impairments in the APPswe/PS1dE9 Alzheimer's Disease Mouse Model. J Nutr 153(4):1038-1051 |
| abstractText | BACKGROUND: Alzheimer's disease (AD) is an age-related neurodegenerative disease characterized by amyloid-beta (Abeta) plaques. Systemic inflammation and obesity may exacerbate AD pathogenesis. We previously reported anti-inflammatory and anti-obesity effects of EPA in mice. OBJECTIVES: We aimed to determine whether EPA reduces obesity-associated metabolic dysfunctions and Abeta accumulation in AD amyloidogenic mice. METHODS: Two-mo-old APPswe/PS1dE9 transgenic (TG) mice and non-TG littermates were randomly assigned to low fat (LF; 10% kcal fat), high fat (HF; 45% kcal fat), or EPA (36 g/kg)-supplemented HF diets. Body composition, glucose tolerance, and energy expenditure were measured, and serum and brain metabolic markers were tested 38 wk postintervention. Outcomes were statistically analyzed via 3-factor ANOVA, modeling genotype, sex, and diet interactions. RESULTS: HF-fed males gained more weight than females (Delta = 61 mg; P < 0.001). Compared with LF, HF increased body weights of wild-type (WT) males (Delta = 31 mg; P < 0.001). EPA reduced HF-induced weight gain in WT males (Delta = 24 mg; P = 0.054) but not in females. HF mice showed decreased glucose clearance and respiratory energy compared with LF-fed groups (Delta = -1.31 g/dL; P < 0.001), with no significant effects of EPA. However, EPA conferred metabolic improvements by decreasing serum leptin and insulin (Delta = -2.51 g/mL and Delta = -0.694 ng/mL, respectively compared with HF, P </= 0.05) and increasing adiponectin (Delta = 21.6 ng/mL; P < 0.001). As we expected, TG mice expressed higher serum and brain Abeta than WT mice (Delta = 0.131 ng/mL; P < 0.001 and Delta = 0.56%; P < 0.01, respectively), and EPA reduced serum Abeta(1-40) in TG males compared with HF (Delta = 0.053 ng/mL; P </= 0.05). CONCLUSIONS: To our knowledge, this is the first report that EPA reduces serum Abeta(1-40) in obese AD male mice, warranting further investigations into tissue-specific mechanisms of EPA in AD. |
