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

224 Citations (Scopus)

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 2004

Fingerprint

Caveolin 1
Lipolysis
Cyclic AMP-Dependent Protein Kinases
Adipocytes
Adipose Tissue
Lipid Droplets
Freeze Substitution
Cyclic AMP-Dependent Protein Kinase Catalytic Subunits
Phosphorylation
Adrenergic Agonists
Lipid Metabolism
Molecular Biology
Electron Microscopy
Cytoplasm
Fibroblasts
Perilipin-1

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Cohen, A. W., Razani, B., Schubert, W., Williams, T. M., Wang, X. B., Iyengar, P., ... 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

Role of Caveolin-1 in the Modulation of Lipolysis and Lipid Droplet Formation. / Cohen, Alex W.; Razani, Babak; Schubert, William; Williams, Terence M.; Wang, Xiao Bo; Iyengar, Puneeth; Brasaemle, Dawn L.; Scherer, Philipp E.; Lisanti, Michael P.

In: Diabetes, Vol. 53, No. 5, 05.2004, p. 1261-1270.

Research output: Contribution to journalArticle

Cohen, AW, Razani, B, Schubert, W, Williams, TM, Wang, XB, Iyengar, P, Brasaemle, DL, Scherer, PE & Lisanti, MP 2004, 'Role of Caveolin-1 in the Modulation of Lipolysis and Lipid Droplet Formation', Diabetes, vol. 53, no. 5, pp. 1261-1270. https://doi.org/10.2337/diabetes.53.5.1261
Cohen, Alex W. ; Razani, Babak ; Schubert, William ; Williams, Terence M. ; Wang, Xiao Bo ; Iyengar, Puneeth ; Brasaemle, Dawn L. ; Scherer, Philipp E. ; Lisanti, Michael P. / Role of Caveolin-1 in the Modulation of Lipolysis and Lipid Droplet Formation. In: Diabetes. 2004 ; Vol. 53, No. 5. pp. 1261-1270.
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