Unsaturated fatty acids revert diet-induced hypothalamic inflammation in obesity
Open accessAbstract
BACKGROUND: In experimental models, hypothalamic inflammation is an early and determining factor in the installation and progression of obesity. Pharmacological and gene-based approaches have proven efficient in restraining inflammation and correcting the obese phenotypes. However, the role of nutrients in the modulation of hypothalamic inflammation is unknown. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that, in a mouse model of diet-induced obesity, partial substitution of the fatty acid component of the diet by flax seed oil (rich in C18:3) or olive oil (rich in C18:1) corrects hypothalamic inflammation, hypothalamic and whole body insulin resistance, and body adiposity. In addition, upon icv injection in obese rats, both ω3 and ω9 pure fatty acids reduce spontaneous food intake and body mass gain. These effects are accompanied by the reversal of functional and molecular hypothalamic resistance to leptin/insulin and increased POMC and CART expressions. In addition, both, ω3 and ω9 fatty acids inhibit the AMPK/ACC pathway and increase CPT1 and SCD1 expression in the hypothalamus. Finally, acute hypothalamic injection of ω3 and ω9 fatty acids activate signal transduction through the recently identified GPR120 unsaturated fatty acid receptor. CONCLUSIONS/SIGNIFICANCE: Unsaturated fatty acids can act either as nutrients or directly in the hypothalamus, reverting diet-induced inflammation and reducing body adiposity. These data show that, in addition to pharmacological and genetic approaches, nutrients can also be attractive candidates for controlling hypothalamic inflammation in obesity.
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In rodents, high saturated fat content causes hyperinsulinemia, liver and muscle insulin resistance, and hypothalamic inflammation.
“which in rodents causes hyperinsulinemia, liver and muscle insulin resistance, and hypothalamic inflammation (137–143).”
From The carbohydrate-insulin model: A physiological perspective on the obesity pandemic (2021) · cites this paper as [139]
Substitution of unsaturated fat for saturated fat in these protocols, or ablation of toll-like receptor signaling, reduces metabolic dysfunction and adiposity in rodents.
“Substitution of unsaturated fat for saturated fat in these protocols, or ablation of toll-like receptor signaling, reduces metabolic dysfunction and adiposity (137–143).”
From The carbohydrate-insulin model: A physiological perspective on the obesity pandemic (2021) · cites this paper as [139]
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References 40 · Cited by 381
- Authors
- Cintra, D. E., Ropelle, E. R., Moraes, J. C., Pauli, J. R., Morari, J., de Souza, C. T., Grimaldi, R., Stahl, M., Carvalheira, J. B., Saad, M. J., & Velloso, L. A.
- Affiliations
- Universidade Estadual de Campinas (UNICAMP) (BR)
- Corresponding author
- Velloso, Licio A.
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2012-01-18
- Volume
- 7
- Issue
- 1
- Pages
- e30571
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3261210
- OpenAlex
- W1987520295
- Cited by
- 381
- References
- 40
- Citations by year
- 2026: 8 · 2025: 18 · 2024: 17 · 2023: 21 · 2022: 24 · 2021: 23 · 2020: 26 · 2019: 34 · 2018: 26 · 2017: 39 · 2016: 36 · 2015: 32 · 2014: 29 · 2013: 33 · 2012: 14
- FWCI
- 15.32
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (publishedVersion, other-oa)
- Americanae (AECID Library) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Keywords
- unsaturated fatty acids, hypothalamic inflammation, diet-induced obesity, omega-3 fatty acids, omega-9 fatty acids, linseed oil, olive oil, insulin resistance, leptin resistance, dietary intake, weight gain, proopiomelanocortin, CART, GPR120
- MeSH terms
- Olive Oil, Cocaine- and Amphetamine-Regulated Transcript Protein, Animals, Dietary Fats, Dietary Fats, Unsaturated, Eating, Fatty Acids, Hypothalamus, Inflammation, Insulin Resistance, Male, Nerve Tissue Proteins, Obesity, Plant Oils, Pro-Opiomelanocortin, Immunoblotting, Signal Transduction, Weight Gain, Fatty Acids, Omega-3, Gene Expression, Rats, Wistar, Reverse Transcriptase Polymerase Chain Reaction, Receptors, G-Protein-Coupled, Mice, Rats
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