Eicosapentaenoic Acid Protects against Metabolic Impairments in the APPswe/PS1dE9 Alzheimer's Disease Mouse Model

Mahsa Yavari, Latha Ramalingam, Breanna N. Harris, Chanaka Nadeeshan Kahathuduwa, Angela Chavira, Caroline Biltz, Logan Mounce, Kaylee Alers Maldonado, Shane Scoggin, Yujiao Zu, Nishan Sudheera Kalupahana, Mohammad Yosofvand, Hanna Moussa, Naima Moustaid-Moussa

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1038-1051
Number of pages14
JournalJournal of Nutrition
Issue number4
StatePublished - Apr 2023
Externally publishedYes


  • APP/PS1 mouse model
  • Alzheimer's disease
  • EPA
  • amyloid-beta
  • obesity

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics


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