Role of Caveolin-1 in the Modulation of Lipolysis and Lipid Droplet Formation

Alex W. Cohen, Babak Razani, William Schubert, Terence M. Williams, Xiao Bo Wang, Puneeth Iyengar, Dawn L. Brasaemle, Philipp E. Scherer, Michael P. Lisanti

Research output: Contribution to journalArticle

231 Scopus citations

Abstract

Recently, it was shown that caveolin-1 can be redirected from the cell surface to intracellular lipid droplets in a variety of cell types. Here, we directly address the role of caveolin-1 in lipid droplet formation and breakdown, showing that caveolin-1 null mice exhibit markedly attenuated lipolytic activity. Mechanistically, although the activity of protein kinase A (PKA) was greatly increased in caveolin-1 null adipocytes, the phosphorylation of perilipin was dramatically reduced, indicating that caveolin-1 may facilitate the PKA-mediated phosphorylation of perilipin. In support of this hypothesis, coimmunoprecipitation experiments revealed that treatment with a β3-adrenergic receptor agonist resulted in ligand-induced complex formation between perilipin, caveolin-1, and the catalytic subunit of PKA in wild-type but not in caveolin-1 null fat pads. We also show that caveolin-1 expression is important for efficient lipid droplet formation because caveolin-1 null embryonic fibroblasts stably transfected with perilipin accumulated ∼4.5-fold less lipid than perilipin-transfected wild-type cells. Finally, high-pressure freeze-substitution electron microscopy of adipose tissue revealed dramatic perturbations in the architecture of the "lipid droplet cortex" (the interface between the lipid droplet surface and the cytoplasm) in caveolin-1 null perigonadal adipocytes. Taken together, our data provide the first molecular genetic evidence that caveolin-1 plays a critical functional and structural role in the modulation of both lipid droplet biogenesis and metabolism in vivo.

Original languageEnglish (US)
Pages (from-to)1261-1270
Number of pages10
JournalDiabetes
Volume53
Issue number5
DOIs
StatePublished - May 1 2004

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Cohen, A. W., Razani, B., Schubert, W., Williams, T. M., Wang, X. B., Iyengar, P., Brasaemle, D. L., Scherer, P. E., & Lisanti, M. P. (2004). Role of Caveolin-1 in the Modulation of Lipolysis and Lipid Droplet Formation. Diabetes, 53(5), 1261-1270. https://doi.org/10.2337/diabetes.53.5.1261