Mechanisms of enhanced insulin secretion and sensitivity with n-3 unsaturated fatty acids

J Nutr Biochem. 2015 Jun;26(6):571-84. doi: 10.1016/j.jnutbio.2015.02.001. Epub 2015 Feb 26.


The widespread acceptance that increased dietary n-3 polyunsaturated fatty acids (PUFAs), especially α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), improve health is based on extensive studies in animals, isolated cells and humans. Visceral adiposity is part of the metabolic syndrome, together with insulin resistance, dyslipidemia, hypertension and inflammation. Alleviation of metabolic syndrome requires normalization of insulin release and responses. This review assesses our current knowledge of the mechanisms that allow n-3 PUFAs to improve insulin secretion and sensitivity. EPA has been more extensively studied than either ALA or DHA. The complex actions of EPA include increased G-protein-receptor-mediated release of glucagon-like peptide 1 (GLP-1) from enteroendocrine L-cells in the intestine, up-regulation of the apelin pathway and down-regulation of other control pathways to promote insulin secretion by the pancreatic β-cells, together with suppression of inflammatory responses to adipokines, inhibition of peroxisome proliferator-activated receptor α actions and prevention of decreased insulin-like growth factor-1 secretion to improve peripheral insulin responses. The receptors involved and the mechanisms of action probably differ for ALA and DHA, with antiobesity effects predominating for ALA and anti-inflammatory effects for DHA. Modifying both GLP-1 release and the actions of adipokines by n-3 PUFAs could lead to additive improvements in both insulin secretion and sensitivity.

Keywords: Adipokines; Inflammation; Insulin; Obesity; n-3 polyunsaturated fatty acids.

Publication types

  • Review

MeSH terms

  • Adipokines / metabolism
  • Animals
  • Disease Models, Animal
  • Docosahexaenoic Acids / pharmacology*
  • Down-Regulation
  • Eicosapentaenoic Acid / pharmacology*
  • Glucagon-Like Peptide 1 / metabolism
  • Humans
  • Insulin / metabolism*
  • Insulin Resistance*
  • Insulin Secretion
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / metabolism
  • PPAR alpha / genetics
  • PPAR alpha / metabolism
  • Up-Regulation
  • alpha-Linolenic Acid / pharmacology*


  • Adipokines
  • Insulin
  • PPAR alpha
  • alpha-Linolenic Acid
  • Docosahexaenoic Acids
  • Glucagon-Like Peptide 1
  • Eicosapentaenoic Acid