Fish oil supplementation alleviates metabolic and anxiodepressive effects of diet-induced obesity and associated changes in brain lipid composition in mice
Open accessAbstract
Objective 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.Methods 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.Results 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.Conclusions 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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Chronic saturated high-fat feeding increases saturated fatty acid levels and appreciably decreases polyunsaturated fatty acid levels in the brain of rodents.
“Moreover, chronic saturated high-fat feeding increases saturated fatty acid levels and appreciably decreases PUFA levels in the brain of rodents [49], changes that are likely one means by which saturated dietary fats generate neuroinflammatory responses and mood deficits.”
From The menace of obesity to depression and anxiety prevalence (2022) · cites this paper as [49]
Reversing neuroinflammation via targeted genetic, pharmacological, or dietary approaches that rescue behavioral anomalies supports a causal role of neuroinflammation in obesity-induced neuropathophysiology.
“Reversing neuroinflammation via targeted genetic [96,97], pharmacological [98,99], or dietary [49,100] approaches that rescue behavioral anomalies offers convincing support for a causal role of neuroinflammation in obesity-induced neuropathophysiology.”
From The menace of obesity to depression and anxiety prevalence (2022) · cites this paper as [49]
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- Authors
- Demers, G., Roy, J., Machuca-Parra, A. I., Dashtehei pour, Z., Bairamian, D., Daneault, C., Rosiers, C. D., Ferreira, G., Alquier, T., Fulton, S., & Representative of consortium
- Affiliations
- Centre Hospitalier de l’Université de Montréal (CA)
- Montreal Heart Institute (CA)
- Université de Bordeaux (FR)
- Corresponding author
- Fulton, Stephanie
- ORCID
- Venue
- International Journal of Obesity
- Published
- 2020-06-16
- Volume
- 44
- Issue
- 9
- Pages
- 1936-1945
- ISSN
- 0307-0565 (ISSN-L)
- 1476-5497
- OpenAlex
- W3034793440
- Cited by
- 53
- References
- 61
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 14 · 2023: 8 · 2022: 9 · 2021: 12 · 2020: 1
- FWCI
- 4.74
- Type
- journal article
- Language
- en
- Open access
- green
- hal.inrae.fr
- Licence
- Locations
- International Journal of Obesity (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- HAL (submittedVersion)
- Oskar-Bordeaux (Universite de Bordeaux) (submittedVersion)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Agricultural and Biological Sciences › Aquatic Science › Aquaculture Nutrition and Growth
- Keywords
- fish oil supplementation, omega-3 polyunsaturated fatty acids, diet-induced obesity, high-fat diet, brain lipid composition, docosahexaenoic acid, eicosapentaenoic acid, impaired glucose tolerance, hyperphagia, microglial activation, astrocyte activation, neuroinflammation, mood disorders, energy homeostasis
- MeSH terms
- Adipose Tissue, Animals, Anxiety, Behavior, Animal, Brain, Brain Chemistry, Depression, Fish Oils, Male, Mice, Inbred C57BL, Obesity, Dietary Supplements, Mice, Diet, High-Fat
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