Eicosapentaenoic Acid Protects against Metabolic Impairments in the APPswe/PS1dE9 Alzheimer's Disease Mouse Model
ORCID
Latha Ramalingam: 0000-0002-4856-7327
Document Type
Article
Date
4-2023
Keywords
APP/PS1 mouse model, Alzheimer’s disease, EPA, amyloid-beta, obesity.
Disciplines
Molecular, Genetic, and Biochemical Nutrition
Description/Abstract
Background: Alzheimer's disease (AD) is an age-related neurodegenerative disease characterized by amyloid-β (Aβ) 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 Aβ 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 (Δ = 61 mg; P < 0.001). Compared with LF, HF increased body weights of wild-type (WT) males (Δ = 31 mg; P < 0.001). EPA reduced HF-induced weight gain in WT males (Δ = 24 mg; P = 0.054) but not in females. HF mice showed decreased glucose clearance and respiratory energy compared with LF-fed groups (Δ = -1.31 g/dL; P < 0.001), with no significant effects of EPA. However, EPA conferred metabolic improvements by decreasing serum leptin and insulin (Δ = -2.51 g/mL and Δ = -0.694 ng/mL, respectively compared with HF, P ≤ 0.05) and increasing adiponectin (Δ = 21.6 ng/mL; P < 0.001). As we expected, TG mice expressed higher serum and brain Aβ than WT mice (Δ = 0.131 ng/mL; P < 0.001 and Δ = 0.56%; P < 0.01, respectively), and EPA reduced serum Aβ1-40 in TG males compared with HF (Δ = 0.053 ng/mL; P ≤ 0.05).
Conclusions: To our knowledge, this is the first report that EPA reduces serum Aβ1-40 in obese AD male mice, warranting further investigations into tissue-specific mechanisms of EPA in AD.
Recommended Citation
Yavari M, Ramalingam L, Harris BN, Kahathuduwa CN, Chavira A, Biltz C, Mounce L, Maldonado KA, Scoggin S, Zu Y, Kalupahana NS, Yosofvand M, Moussa H, Moustaid-Moussa N. Eicosapentaenoic Acid Protects against Metabolic Impairments in the APPswe/PS1dE9 Alzheimer's Disease Mouse Model. J Nutr. 2023 Apr;153(4):1038-1051. doi: 10.1016/j.tjnut.2023.01.030. Epub 2023 Feb 1. PMID: 36781072; PMCID: PMC10273166.
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This work is licensed under a Creative Commons Attribution 4.0 International License.
