Zinc alpha2 glycoprotein promotes browning in adipocytes

Biochem Biophys Res Commun. 2018 Feb 5;496(2):287-293. doi: 10.1016/j.bbrc.2018.01.039. Epub 2018 Jan 6.

Abstract

Recent studies have highlighted recruiting and activating brite adipocytes in WAT (so-called "browning") would be an attractive anti-obesity strategy. Zinc alpha2 glycoprotein (ZAG) as an important adipokine, is reported to ameliorate glycolipid metabolism and lose body weight in obese mice. However whether the body reducing effect mediated by browning programme remains unclear. Here, we show that overexpression of ZAG in 3T3-L1 adipocytes enhanced expression of brown fat-specific markers (UCP-1, PRDM16 and CIDEA), mitochondrial biogenesis genes (PGC-1α, NRF-1/2 and mtTFA) and the key lipid metabolism lipases (ATGL, HSL, CPT1-A and p-acyl-CoA carboxylase). Additionally, those effects were dramaticlly abolished by H89/SB203580, revealing ZAG-induced browning depend on PKA and p38 MAPK signaling. Overall, our findings suggest that ZAG is a candidate therapeutic agent against obesity via induction of brown fat-like phenotype in white adipocytes.

Keywords: Browning; Mitochondrial biogenesis; Obesity; Zinc alpha2 glycoprotein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes, Brown / cytology
  • Adipocytes, Brown / drug effects
  • Adipocytes, Brown / metabolism*
  • Adipokines
  • Animals
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism
  • Carbon-Carbon Ligases / genetics
  • Carbon-Carbon Ligases / metabolism
  • Carnitine O-Palmitoyltransferase / genetics
  • Carnitine O-Palmitoyltransferase / metabolism
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Cyclic AMP-Dependent Protein Kinases / genetics
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation*
  • Glycoproteins / genetics*
  • Glycoproteins / metabolism
  • Imidazoles / pharmacology
  • Isoquinolines / pharmacology
  • Lipase / genetics
  • Lipase / metabolism
  • Lipid Metabolism / genetics*
  • Mice
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism
  • Nuclear Respiratory Factor 1 / genetics
  • Nuclear Respiratory Factor 1 / metabolism
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / genetics
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism
  • Pyridines / pharmacology
  • Signal Transduction
  • Sulfonamides / pharmacology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Uncoupling Protein 1 / genetics
  • Uncoupling Protein 1 / metabolism

Substances

  • AZGP1 protein, mouse
  • Adipokines
  • Apoptosis Regulatory Proteins
  • Carrier Proteins
  • Cidea protein, mouse
  • DNA-Binding Proteins
  • Glycoproteins
  • Imidazoles
  • Isoquinolines
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • Nrf1 protein, mouse
  • Nuclear Respiratory Factor 1
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, mouse
  • Prdm16 protein, mouse
  • Pyridines
  • Sulfonamides
  • Transcription Factors
  • Ucp1 protein, mouse
  • Uncoupling Protein 1
  • CPT1B protein, mouse
  • Carnitine O-Palmitoyltransferase
  • Cyclic AMP-Dependent Protein Kinases
  • Lipase
  • PNPLA2 protein, mouse
  • Carbon-Carbon Ligases
  • acyl-CoA carboxylase
  • N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide
  • SB 203580