Central agonism of GPR120 acutely inhibits food intake and food reward and chronically suppresses anxiety-like behavior in mice
Open accessAbstract
BACKGROUND: GPR120 (FFAR4) is a G-protein coupled receptor implicated in the development of obesity and the antiinflammatory and insulin-sensitizing effects of omega-3 (ω-3) polyunsaturated fatty acids. Increasing central ω-3 polyunsaturated fatty acid levels has been shown to have both anorectic and anxiolytic actions. Despite the strong clinical interest in GPR120, its role in the brain is largely unknown, and thus we sought to determine the impact of central GPR120 pharmacological activation on energy balance, food reward, and anxiety-like behavior. METHODS: Male C57Bl/6 mice with intracerebroventricular cannulae received a single injection (0.1 or 1 µM) or continuous 2-week infusion (1 µM/d; mini-pump) of a GPR120 agonist or vehicle. Free-feeding intake, operant lever-pressing for palatable food, energy expenditure (indirect calorimetry), and body weight were measured. GPR120 mRNA expression was measured in pertinent brain areas. Anxiety-like behavior was assessed in the elevated-plus maze and open field test. RESULTS: GPR120 agonist injections substantially reduced chow intake during 4 hours postinjection, suppressed the rewarding effects of high-fat/-sugar food, and blunted approach-avoidance behavior in the open field. Conversely, prolonged central GPR120 agonist infusions reduced anxiety-like behavior in the elevated-plus maze and open field, yet failed to affect free-feeding intake, energy expenditure, and body weight on a high-fat diet. CONCLUSION: Acute reductions in food intake and food reward suggest that GPR120 could mediate the effects of central ω-3 polyunsaturated fatty acids to inhibit appetite. The anxiolytic effect elicited by GPR120 agonist infusions favors the testing of compounds that can enter the brain to activate GPR120 for the mitigation of anxiety.
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Central GPR120 agonism can suppress anxiety-like behaviors in mice exposed to a saturated high-fat diet.
“Correspondingly, central GPR120 agonism can suppress anxiety-like behaviors in mice exposed to a saturated HFD [51].”
From The menace of obesity to depression and anxiety prevalence (2022) · cites this paper as [51]
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The menace of obesity to depression and anxiety prevalence
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“The effects of DIO on the hippocampus have received considerable attention because of the well-reported effects of HFD to elicit cognitive and emotional impairments [102].”
BackgroundInfluentialSelf-citationInterplay between the gut-brain axis, obesity and cognitive function
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Liu, T., Ji, R.-L., & Tao, Y.-X. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2021.108044 · Cited by 34 · see citing works
- Authors
- Auguste, S., Fisette, A., Fernandes, M. F., Hryhorczuk, C., Poitout, V., Alquier, T., & Fulton, S.
- Affiliations
- Université de Montréal (CA)
- Corresponding author
- Auguste, Stéphanie
- ORCID
- Venue
- International Journal of Neuropsychopharmacology
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-02-17
- Volume
- 19
- Issue
- 7
- Pages
- pyw014
- ISSN
- 1461-1457 (ISSN-L)
- 1469-5111
- PMC
- PMC4966276
- OpenAlex
- W2292799020
- Cited by
- 59
- References
- 44
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 7 · 2023: 4 · 2022: 5 · 2021: 12 · 2020: 7 · 2019: 7 · 2018: 5 · 2017: 3 · 2016: 2
- FWCI
- 3.62
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc
- Locations
- The International Journal of Neuropsychopharmacology (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Canadian Diabetes Association
- Université de Montréal
- Canadian Institutes of Health Research
- Natural Sciences and Engineering Research Council of Canada
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Keywords
- GPR120, free fatty acid receptor 4, omega-3 polyunsaturated fatty acids, dietary intake, food reward, anxiety-like behavior, anxiolytic effects, appetite regulation, energy balance, high-fat diet, intracerebroventricular infusion, G protein-coupled receptor agonists
- MeSH terms
- Animals, Anxiety, Benzofurans, Body Weight, Conditioning, Operant, Eating, Energy Metabolism, Male, Motor Activity, Reward, Sulfones, Maze Learning, Receptors, G-Protein-Coupled, Mice, Infusions, Intraventricular, Diet, High-Fat
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