Diets Containing α-Linolenic (ω3) or Oleic (ω9) Fatty Acids Rescues Obese Mice From Insulin Resistance

Endocrinology. 2015 Nov;156(11):4033-46. doi: 10.1210/en.2014-1880. Epub 2015 Aug 17.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism
  • Animals
  • Dietary Fats / administration & dosage
  • Dietary Fats / pharmacology*
  • Glucose / metabolism
  • Homeostasis / drug effects
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / pharmacology
  • Immunoblotting
  • Inflammation / metabolism
  • Inflammation / physiopathology
  • Inflammation / prevention & control
  • Insulin / administration & dosage
  • Insulin / pharmacology
  • Insulin Resistance*
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Mice, Obese
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism
  • Obesity / metabolism
  • Obesity / physiopathology
  • Obesity / prevention & control*
  • Oleic Acid / administration & dosage
  • Oleic Acid / pharmacology*
  • RNA Interference
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism
  • Signal Transduction / drug effects
  • Weight Gain / drug effects
  • alpha-Linolenic Acid / administration & dosage
  • alpha-Linolenic Acid / pharmacology*


  • Dietary Fats
  • FFAR4 protein, mouse
  • Ffar1 protein, mouse
  • Hypoglycemic Agents
  • Insulin
  • Receptors, G-Protein-Coupled
  • alpha-Linolenic Acid
  • Oleic Acid
  • Glucose