Lipocalin 2 produces insulin resistance and can be upregulated by glucocorticoids in human adipose tissue

Mol Cell Endocrinol. 2016 May 15:427:124-32. doi: 10.1016/j.mce.2016.03.011. Epub 2016 Mar 10.

Abstract

The adipokine lipocalin 2 is linked to obesity and metabolic disorders. However, its role in human adipose tissue glucose and lipid metabolism is not explored. Here we show that the synthetic glucocorticoid dexamethasone dose-dependently increased lipocalin 2 gene expression in subcutaneous and omental adipose tissue from pre-menopausal females, while it had no effect in post-menopausal females or in males. Subcutaneous adipose tissue from both genders treated with recombinant human lipocalin 2 showed a reduction in protein levels of GLUT1 and GLUT4 and in glucose uptake in isolated adipocytes. In subcutaneous adipose tissue, lipocalin 2 increased IL-6 gene expression whereas expression of PPARγ and adiponectin was reduced. Our findings suggest that lipocalin 2 can contribute to insulin resistance in human adipose tissue. In pre-menopausal females, it may partly mediate adverse metabolic effects exerted by glucocorticoid excess.

Keywords: Glucocorticoids; Human adipose tissue; Insulin resistance; Lipocalin 2; PPARγ; Type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiponectin / genetics
  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism*
  • Adult
  • Aged
  • Dexamethasone / pharmacology
  • Female
  • Glucocorticoids / chemical synthesis
  • Glucocorticoids / physiology*
  • Glucose / metabolism
  • Humans
  • Insulin Resistance*
  • Lipocalin-2 / metabolism
  • Lipocalin-2 / physiology*
  • Male
  • Middle Aged
  • PPAR gamma / metabolism
  • Recombinant Proteins / pharmacology
  • Subcutaneous Fat / drug effects
  • Subcutaneous Fat / metabolism
  • Up-Regulation
  • Young Adult

Substances

  • Adiponectin
  • Glucocorticoids
  • Lipocalin-2
  • PPAR gamma
  • Recombinant Proteins
  • Dexamethasone
  • Glucose