Diets containing α-linolenic (ω3) or oleic (ω9) fatty acids rescues obese mice from insulin resistance
Abstract
Subclinical systemic inflammation is a hallmark of obesity and insulin resistance. The results obtained from a number of experimental studies suggest that targeting different components of the inflammatory machinery may result in the improvement of the metabolic phenotype. Unsaturated fatty acids exert antiinflammatory activity through several distinct mechanisms. Here, we tested the capacity of ω3 and ω9 fatty acids, directly from their food matrix, to exert antiinflammatory activity through the G protein-coupled receptor (GPR)120 and GPR40 pathways. GPR120 was activated in liver, skeletal muscle, and adipose tissues, reverting inflammation and insulin resistance in obese mice. Part of this action was also mediated by GPR40 on muscle, as a novel mechanism described. Pair-feeding and immunoneutralization experiments reinforced the pivotal role of GPR120 as a mediator in the response to the nutrients. The improvement in insulin sensitivity in the high-fat substituted diets was associated with a marked reduction in tissue inflammation, decreased macrophage infiltration, and increased IL-10 levels. Furthermore, improved glucose homeostasis was accompanied by the reduced expression of hepatic gluconeogenic enzymes and reduced body mass. Thus, our data indicate that GPR120 and GPR40 play a critical role as mediators of the beneficial effects of dietary unsaturated fatty acids in the context of obesity-induced insulin resistance.
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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 [140]
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 [140]
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Targeting FFA1 and FFA4 receptors in cancer-induced cachexia
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Self-citationShort-Term Combined Exercise Improves Inflammatory Profile in the Retina of Obese Mice
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Self-citationPriming Effect of a Morning Meal on Hepatic Glucose Disposition Later in the Day
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A plasma fatty acid profile associated to type 2 diabetes development: from the CORDIOPREV study
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Understanding the appetite modulation pathways: The role of the FFA1 and FFA4 receptors
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Self-citationShort-term combined training reduces hepatic steatosis and improves hepatic insulin signaling
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Self-citationG protein-coupled receptors: Key molecules in metabolic associated fatty liver disease development
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PA and OA induce abnormal glucose metabolism by inhibiting KLF15 in adipocytes
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FOXO1 is downregulated in obese mice subjected to short‐term strength training
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Supplementation with GPR120 (Ffar4) ligand omega-3 does not improve survival in murine sepsis models
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The influence of diet, age, and obesity on hypothalamic omega-3 fatty acid transporter MFSD2a
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Advances in Research on α-Linolenic Acid in Metabolic Syndrome and Related Cardiovascular Injury
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Hypothalamic Injury: Fish Oil to the Rescue!
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Additional file 1 of PA and OA induce abnormal glucose metabolism by inhibiting KLF15 in adipocytes
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- Authors
- Oliveira, V., Marinho, R., Vitorino, D., Santos, G. A., Moraes, J. C., Dragano, N., Sartori-Cintra, A., Pereira, L., Catharino, R. R., da Silva, A. S. R., Ropelle, E. R., Pauli, J. R., De Souza, C. T., Velloso, L. A., & Cintra, D. E.
- Affiliations
- Universidade Estadual de Campinas (UNICAMP) (BR)
- Molecular Biology of Exercise (R.M., L.P., A.S.R.d.S., E.R.R., J.R.P.), School of Applied Sciences, State University of Campinas, Campinas, Brazil 13083-887
- Laboratory of Exercise Biochemistry and Physiology (C.T.D.S.), Health Sciences Unit, Universidade do Extremo Sul Catarinense Criciúma, Brazil 88806-000
- Corresponding author
- Cintra, D. E.
- ORCID
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2015-08-17
- Volume
- 156
- Issue
- 11
- Pages
- 4033-4046
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2131862502
- Cited by
- 102
- References
- 32
- Citations by year
- 2026: 3 · 2025: 9 · 2023: 7 · 2022: 11 · 2021: 23 · 2020: 15 · 2019: 10 · 2018: 5 · 2017: 13 · 2016: 6
- FWCI
- 7.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Fundação de Amparo à Pesquisa do Estado de São Paulo (12/07129-6)
- Universidade Estadual de Campinas
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Keywords
- alpha-linolenic acid, oleic acid, omega-3 fatty acids, omega-9 fatty acids, obesity, insulin resistance, GPR120, GPR40, G protein-coupled receptors, anti-inflammatory activity, systemic inflammation, macrophage infiltration, IL-10, hepatic gluconeogenesis, glucose homeostasis, skeletal muscle, adipose tissue, high-fat diet, pair feeding, immunoneutralization
- MeSH terms
- Adipose Tissue, Animals, Dietary Fats, Glucose, Homeostasis, Hypoglycemic Agents, Inflammation, Insulin, Insulin Resistance, Liver, Male, Mice, Obese, Obesity, Immunoblotting, Signal Transduction, Weight Gain, alpha-Linolenic Acid, Muscle, Skeletal, Oleic Acid, RNA Interference, Receptors, G-Protein-Coupled
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