Flaxseed Oil Alleviates Chronic HFD-Induced Insulin Resistance Through Remodeling Lipid Homeostasis in Obese Adipose Tissue

J Agric Food Chem. 2017 Nov 8;65(44):9635-9646. doi: 10.1021/acs.jafc.7b03325. Epub 2017 Oct 25.


Emerging evidence suggests that higher circulating long-chain n-3 polyunsaturated fatty acids (n-3PUFA) levels were intimately associated with lower prevalence of obesity and insulin resistance. However, the understanding of bioactivity and potential mechanism of α-linolenic acid-rich flaxseed oil (ALA-FO) against insulin resistance was still limited. This study evaluated the effect of FO on high-fat diet (HFD)-induced insulin resistance in C57BL/6J mice focused on adipose tissue lipolysis. Mice after HFD feeding for 16 weeks (60% fat-derived calories) exhibited systemic insulin resistance, which was greatly attenuated by medium dose of FO (M-FO), paralleling with differential accumulation of ALA and its n-3 derivatives across serum lipid fractions. Moreover, M-FO was sufficient to effectively block the metabolic activation of adipose tissue macrophages (ATMs), thereby improving adipose tissue insulin signaling. Importantly, suppression of hypoxia-inducible factors HIF-1α and HIF-2α were involved in FO-mediated modulation of adipose tissue lipolysis, accompanied by specific reconstitution of n-3PUFA within adipose tissue lipid fractions.

Keywords: ATMs metabolic activation; adipose tissue lipolysis; flaxseed oil; hypoxia; insulin resistance.

MeSH terms

  • Adipose Tissue / metabolism*
  • Animals
  • Diet, High-Fat / adverse effects*
  • Humans
  • Insulin / metabolism
  • Insulin Resistance*
  • Linseed Oil / metabolism*
  • Lipid Metabolism
  • Lipids / blood
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Obesity / diet therapy*
  • Obesity / genetics
  • Obesity / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • HIF-2 protein, mouse
  • Insulin
  • Lipids
  • Transcription Factors
  • Linseed Oil