Desnutrin/ATGL is regulated by AMPK and is required for a brown adipose phenotype

Cell Metab. 2011 Jun 8;13(6):739-48. doi: 10.1016/j.cmet.2011.05.002.

Abstract

While fatty acids (FAs) released by white adipose tissue (WAT) provide energy for other organs, lipolysis is also critical in brown adipose tissue (BAT), generating FAs for oxidation and UCP-1 activation for thermogenesis. Here we show that adipose-specific ablation of desnutrin/ATGL in mice converts BAT to a WAT-like tissue. These mice exhibit severely impaired thermogenesis with increased expression of WAT-enriched genes but decreased BAT genes, including UCP-1 with lower PPARα binding to its promoter, revealing the requirement of desnutrin-catalyzed lipolysis for maintaining a BAT phenotype. We also show that desnutrin is phosphorylated by AMPK at S406, increasing TAG hydrolase activity, and provide evidence for increased lipolysis by AMPK phosphorylation of desnutrin in adipocytes and in vivo. Despite adiposity and impaired BAT function, desnutrin-ASKO mice have improved hepatic insulin sensitivity with lower DAG levels. Overall, desnutrin is phosphorylated/activated by AMPK to increase lipolysis and brings FA oxidation and UCP-1 induction for thermogenesis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenylate Kinase / metabolism*
  • Adipose Tissue, Brown / metabolism
  • Adipose Tissue, White / metabolism
  • Adiposity / genetics
  • Animals
  • Cells, Cultured
  • Enzyme Assays
  • Gene Knockout Techniques
  • Ion Channels / genetics
  • Ion Channels / metabolism
  • Lipase / genetics*
  • Lipase / metabolism
  • Lipolysis / genetics
  • Male
  • Mice
  • Mice, Obese
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • Phosphorylation
  • Protein Processing, Post-Translational*
  • Thermogenesis
  • Uncoupling Protein 1

Substances

  • Ion Channels
  • Mitochondrial Proteins
  • Ucp1 protein, mouse
  • Uncoupling Protein 1
  • Adenylate Kinase
  • Lipase
  • PNPLA2 protein, mouse