Omega 3 rich diet modulates energy metabolism via GPR120-Nrf2 crosstalk in a novel antioxidant mouse model

Biochim Biophys Acta Mol Cell Biol Lipids. 2019 Apr;1864(4):466-488. doi: 10.1016/j.bbalip.2019.01.002. Epub 2019 Jan 16.


With obesity rates reaching epidemic proportions, more studies concentrated on reducing the risk and treating this epidemic are vital. Redox stress is an important metabolic regulator involved in the pathophysiology of cardiovascular disease, Type 2 diabetes, and obesity. Oxygen and nitrogen-derived free radicals alter glucose and lipid homeostasis in key metabolic tissues, leading to increases in risk of developing metabolic syndrome. Oxidants derived from dietary fat differ in their metabolic regulation, with numerous studies showing benefits from a high omega 3 rich diet compared to the frequently consumed "western diet" rich in saturated fat. Omega 3 (OM3) fatty acids improve lipid profile, lower inflammation, and ameliorate insulin resistance, possibly through maintaining redox homeostasis. This study is based on the hypothesis that altering endogenous antioxidant production and/or increasing OM3 rich diet consumption will improve energy metabolism and maintain insulin sensitivity. We tested the comparative metabolic effects of a diet rich in saturated fat (HFD) and an omega 3-enriched diet (OM3) in the newly developed 'stress-less' mice model that overexpresses the endogenous antioxidant catalase. Eight weeks of dietary intervention showed that mice overexpressing endogenous catalase compared to their wild-type controls when fed an OM3 enriched diet, in contrast to HFD, activated GPR120-Nrf2 cross-talk to maintain balanced energy metabolism, normal circadian rhythm, and insulin sensitivity. These findings suggest that redox regulation of GPR120/FFAR4 might be an important target in reducing risk of metabolic syndrome and associated diseases.

Keywords: Adipose tissue; Catalase; Diet-induced obesity; Redox stress.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Composition / drug effects
  • Body Weight / drug effects
  • Catalase / genetics
  • Catalase / metabolism
  • Diet, High-Fat / adverse effects*
  • Dietary Fats / administration & dosage
  • Dietary Fats / pharmacology
  • Disease Models, Animal
  • Energy Metabolism / drug effects*
  • Fatty Acids, Omega-3 / administration & dosage*
  • Fatty Acids, Omega-3 / pharmacology
  • Insulin Resistance
  • Mice
  • NF-E2-Related Factor 2 / metabolism*
  • Oxidation-Reduction / drug effects*
  • Receptors, G-Protein-Coupled / metabolism*


  • Dietary Fats
  • FFAR4 protein, mouse
  • Fatty Acids, Omega-3
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • Receptors, G-Protein-Coupled
  • Catalase