Acetylation of Cavin-1 Promotes Lipolysis in White Adipose Tissue

Mol Cell Biol. 2017 Jul 28;37(16):e00058-17. doi: 10.1128/MCB.00058-17. Print 2017 Aug 15.

Abstract

White adipose tissue (WAT) serves as a reversible energy storage depot in the form of lipids in response to nutritional status. Cavin-1, an essential component in the biogenesis of caveolae, is a positive regulator of lipolysis in adipocytes. However, molecular mechanisms of cavin-1 in the modulation of lipolysis remain poorly understood. Here, we showed that cavin-1 was acetylated at lysines 291, 293, and 298 (3K), which were under nutritional regulation in WAT. We further identified GCN5 as the acetyltransferase and Sirt1 as the deacetylase of cavin-1. Acetylation-mimetic 3Q mutants of cavin-1 augmented fat mobilization in 3T3-L1 adipocytes and zebrafish. Mechanistically, acetylated cavin-1 preferentially interacted with hormone-sensitive lipase and recruited it to the caveolae, thereby promoting lipolysis. Our findings shed light on the essential role of cavin-1 in regulating lipolysis in an acetylation-dependent manner in WAT.

Keywords: HSL; WAT; acetylation; cavin-1; lipolysis.

MeSH terms

  • 3T3-L1 Cells
  • Acetylation / drug effects
  • Adipose Tissue, White / drug effects
  • Adipose Tissue, White / metabolism*
  • Amino Acid Sequence
  • Animals
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • HEK293 Cells
  • Humans
  • Lipase / metabolism
  • Lipolysis* / drug effects
  • Lysine / metabolism
  • Male
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Niacinamide / pharmacology
  • Protein Binding / drug effects
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / metabolism*
  • Sirtuin 1 / metabolism
  • Zebrafish
  • p300-CBP Transcription Factors / metabolism

Substances

  • Cavin1 protein, mouse
  • Membrane Proteins
  • RNA-Binding Proteins
  • Niacinamide
  • p300-CBP Transcription Factors
  • p300-CBP-associated factor
  • Lipase
  • Sirtuin 1
  • Lysine