Zinc-α2-glycoprotein promotes browning of white adipose tissue in cold-exposed male mice

Mol Cell Endocrinol. 2020 Feb 5:501:110669. doi: 10.1016/j.mce.2019.110669. Epub 2019 Nov 29.

Abstract

The promotion of white adipose tissue (WAT) browning has emerged as a promising therapeutic target to increase energy expenditure and decrease weight gain. Zinc-α2-glycoprotein (ZAG) is a newly identified adipokine that regulates lipid metabolism. It shows high expression in brown adipose tissue (BAT), but whether ZAG plays a key role in the browning of white adipose tissue is still largely unclear. In the present study, we explored the relationship between ZAG and the browning of WAT in cold-exposed ZAG knockout (KO) mice and 3T3-L1 adipocytes with overexpressed ZAG. The results showed that cold stress induced marked accumulation of ZAG in wild type (WT) mice. Additionally, ZAG deficiency inhibited the loss of body weight and adipose tissue weight in cold stressed mice. ZAG KO mice were resistant to cold-induced expression of browning markers and energy metabolism in WAT. Furthermore, replenishment ZAG plasmid improved the reduction in cold-induced browning of WAT in ZAG KO mice. In vitro, ZAG overexpression promoted browning and mitochondrial biogenesis and increased the expression of β3-AR and P-P38 in 3T3-L1 adipocytes. These findings demonstrate that ZAG can promote the browning of white adipose tissue and can serve as a potential therapeutic target for treating metabolic diseases such as obesity.

Keywords: Cold-exposed mice; Mitochondrial biogenesis; WAT browning; ZAG.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / metabolism
  • Adipocytes / physiology
  • Adipokines / metabolism*
  • Adipose Tissue, Brown / metabolism*
  • Adipose Tissue, Brown / physiology
  • Adipose Tissue, White / metabolism*
  • Adipose Tissue, White / physiology
  • Animals
  • Cell Line
  • Cold-Shock Response / physiology*
  • Energy Metabolism / physiology
  • Lipid Metabolism / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Obesity / metabolism
  • Zinc / metabolism

Substances

  • AZGP1 protein, mouse
  • Adipokines
  • Zinc