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Animal Models

Fish oil supplementation alleviates metabolic and anxiodepressive effects of diet-induced obesity and associated changes in brain lipid composition in mice



Obesity significantly elevates the odds of developing mood disorders. Chronic consumption of a saturated high-fat diet (HFD) elicits anxiodepressive behavior in a manner linked to metabolic dysfunction and neuroinflammation in mice. Dietary omega-3 polyunsaturated fatty acids (n-3 PUFA) can improve both metabolic and mood impairments by relieving inflammation. Despite these findings, the effects of n-3 PUFA supplementation on energy homeostasis, anxiodepressive behavior, brain lipid composition, and gliosis in the diet-induced obese state are unclear.


Male C57Bl/6J mice were fed a saturated high-fat diet (HFD) or chow for 20 weeks. During the last 5 weeks mice received daily gavage (“supplementation”) of fish oil (FO) enriched with equal amounts of docosahexaenoic (DHA) and eicosapentaenoic acid (EPA) or control corn oil. Food intake and body weight were measured throughout while additional metabolic parameters and anxiety- and despair-like behavior (elevated-plus maze, light–dark box, and forced swim tasks) were evaluated during the final week of supplementation. Forebrain lipid composition and markers of microglia activation and astrogliosis were assessed by gas chromatography–mass spectrometry and real-time PCR, respectively.


Five weeks of FO supplementation corrected glucose intolerance and attenuated hyperphagia in HFD-induced obese mice without affecting adipose mass. FO supplementation also defended against the anxiogenic and depressive-like effects of HFD. Brain lipids, particularly anti-inflammatory PUFA, were diminished by HFD, whereas FO restored levels beyond control values. Gene expression markers of brain reactive gliosis were supressed by FO.


Supplementing a saturated HFD with FO rich in EPA and DHA corrects glucose intolerance, inhibits food intake, suppresses anxiodepressive behaviors, enhances anti-inflammatory brain lipids, and dampens indices of brain gliosis in obese mice. Together, these findings support increasing dietary n-3 PUFA for the treatment of metabolic and mood disturbances associated with excess fat intake and obesity.

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Fig. 1: Fish oil supplementation protects against diet-induced glucose intolerance and attenuates hyperphagia without affecting body composition.
Fig. 2: Fish oil supplementation alleviates anxiety- and despair-like behavior triggered by a saturated high-fat diet and obesity.
Fig. 3: Forebrain lipid composition changes associated with saturated high-fat feeding and fish oil supplementation.
Fig. 4: Fish oil supplementation suppresses forebrain markers of gliosis.


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This work was supported by grants from the Natural Sciences and Engineering Research Council of Canada to SF, Merck Sharp Dohme Corp to SF, TA, and CDR and Réseau cardiométabolique, diabète & obésité from Fonds de Recherche Québec-Santé (CMDO-FRQS) to TA and CDR. GD was supported by a FRQS graduate fellowship, JR by a FRQS postdoctoral fellowship, GF by an INRA fund for mobility/sabbatical stay, and SF and TA are supported by FRQS senior salary awards.

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Correspondence to Stephanie Fulton.

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Demers, G., Roy, J., Machuca-Parra, A.I. et al. Fish oil supplementation alleviates metabolic and anxiodepressive effects of diet-induced obesity and associated changes in brain lipid composition in mice. Int J Obes 44, 1936–1945 (2020).

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