HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cohen, A. W. Articles by Lisanti, M. P. Search for Related Content PubMed PubMed Citation Articles by Cohen, A. W. Articles by Lisanti, M. P. Social Bookmarking                What's this?

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

¹ Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York
² Albert Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, New York
³ Departments of Cell Biology and Medicine, Division of Endocrinology and Diabetes Research and Training Center, Albert Einstein College of Medicine, Bronx, New York
⁴ Department of Nutritional Sciences, Rutgers, the State University of New Jersey, New Brunswick, New Jersey

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 ß₃-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.

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				K. Jaworski, E. Sarkadi-Nagy, R. E. Duncan, M. Ahmadian, and H. S. Sul Regulation of Triglyceride Metabolism. * IV. Hormonal regulation of lipolysis in adipose tissue Am J Physiol Gastrointest Liver Physiol, July 1, 2007; 293(1): G1 - G4. [Abstract] [Full Text] [PDF]

				S. J. Nixon, A. Carter, J. Wegner, C. Ferguson, M. Floetenmeyer, J. Riches, B. Key, M. Westerfield, and R. G. Parton Caveolin-1 is required for lateral line neuromast and notochord development J. Cell Sci., July 1, 2007; 120(13): 2151 - 2161. [Abstract] [Full Text] [PDF]

				S. Y. Cho, E. S. Shin, P. J. Park, D. W. Shin, H. K. Chang, D. Kim, H. H. Lee, J. H. Lee, S. H. Kim, M. J. Song, et al. Identification of Mouse Prp19p as a Lipid Droplet-associated Protein and Its Possible Involvement in the Biogenesis of Lipid Droplets J. Biol. Chem., January 26, 2007; 282(4): 2456 - 2465. [Abstract] [Full Text] [PDF]

				M. E. Trujillo and P. E. Scherer Adipose Tissue-Derived Factors: Impact on Health and Disease Endocr. Rev., December 1, 2006; 27(7): 762 - 778. [Abstract] [Full Text] [PDF]

				Z. H. Huang, C. A. Reardon, and T. Mazzone Endogenous ApoE Expression Modulates Adipocyte Triglyceride Content and Turnover Diabetes, December 1, 2006; 55(12): 3394 - 3402. [Abstract] [Full Text] [PDF]

				A. F. El-Yazbi, W. J. Cho, R. Schulz, and E. E. Daniel Caveolin-1 knockout alters beta-adrenoceptors function in mouse small intestine Am J Physiol Gastrointest Liver Physiol, December 1, 2006; 291(6): G1020 - G1030. [Abstract] [Full Text] [PDF]

				S. Viswanadha and C. Londos Optimized conditions for measuring lipolysis in murine primary adipocytes J. Lipid Res., August 1, 2006; 47(8): 1859 - 1864. [Abstract] [Full Text] [PDF]

				M. Beller, D. Riedel, L. Jansch, G. Dieterich, J. Wehland, H. Jackle, and R. P. Kuhnlein Characterization of the Drosophila Lipid Droplet Subproteome Mol. Cell. Proteomics, June 1, 2006; 5(6): 1082 - 1094. [Abstract] [Full Text] [PDF]

				D. Binns, T. Januszewski, Y. Chen, J. Hill, V. S. Markin, Y. Zhao, C. Gilpin, K. D. Chapman, R. G.W. Anderson, and J. M. Goodman An intimate collaboration between peroxisomes and lipid bodies J. Cell Biol., May 30, 2006; (2006) jcb.200511125. [Abstract] [Full Text] [PDF]

				A. Marcinkiewicz, D. Gauthier, A. Garcia, and D. L. Brasaemle The Phosphorylation of Serine 492 of Perilipin A Directs Lipid Droplet Fragmentation and Dispersion J. Biol. Chem., April 28, 2006; 281(17): 11901 - 11909. [Abstract] [Full Text] [PDF]

				S. Vankoningsloo, A. De Pauw, A. Houbion, S. Tejerina, C. Demazy, F. de Longueville, V. Bertholet, P. Renard, J. Remacle, P. Holvoet, et al. CREB activation induced by mitochondrial dysfunction triggers triglyceride accumulation in 3T3-L1 preadipocytes J. Cell Sci., April 1, 2006; 119(7): 1266 - 1282. [Abstract] [Full Text] [PDF]

				A. M. Levin, J. G. Coroneus, M. J. Cocco, and G. A. Weiss Exploring the interaction between the protein kinase A catalytic subunit and caveolin-1 scaffolding domain with shotgun scanning, oligomer complementation, NMR, and docking Protein Sci., March 1, 2006; 15(3): 478 - 486. [Abstract] [Full Text] [PDF]

				H.-P. H. Moore, R. B. Silver, E. P. Mottillo, D. A. Bernlohr, and J. G. Granneman Perilipin Targets a Novel Pool of Lipid Droplets for Lipolytic Attack by Hormone-sensitive Lipase J. Biol. Chem., December 30, 2005; 280(52): 43109 - 43120. [Abstract] [Full Text] [PDF]

				H. Robenek, M. J. Robenek, and D. Troyer PAT family proteins pervade lipid droplet cores J. Lipid Res., June 1, 2005; 46(6): 1331 - 1338. [Abstract] [Full Text] [PDF]

				D. C. Adler-Wailes, H. Liu, F. Ahmad, N. Feng, C. Londos, V. Manganiello, and J. A. Yanovski Effects of the Human Immunodeficiency Virus-Protease Inhibitor, Ritonavir, on Basal and Catecholamine-Stimulated Lipolysis J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3251 - 3261. [Abstract] [Full Text] [PDF]

				F. Capozza, T. P. Combs, A. W. Cohen, Y.-R. Cho, S.-Y. Park, W. Schubert, T. M. Williams, D. L. Brasaemle, L. A. Jelicks, P. E. Scherer, et al. Caveolin-3 knockout mice show increased adiposity and whole body insulin resistance, with ligand-induced insulin receptor instability in skeletal muscle Am J Physiol Cell Physiol, June 1, 2005; 288(6): C1317 - C1331. [Abstract] [Full Text] [PDF]

				S. Chung, J. M. Brown, M. B. Sandberg, and M. McIntosh Trans-10,cis-12 CLA increases adipocyte lipolysis and alters lipid droplet-associated proteins: role of mTOR and ERK signaling J. Lipid Res., May 1, 2005; 46(5): 885 - 895. [Abstract] [Full Text] [PDF]

				P. B. Snyder, J. M. Esselstyn, K. Loughney, S. L. Wolda, and V. A. Florio The role of cyclic nucleotide phosphodiesterases in the regulation of adipocyte lipolysis J. Lipid Res., March 1, 2005; 46(3): 494 - 503. [Abstract] [Full Text] [PDF]

				A. W. Cohen, W. Schubert, D. L. Brasaemle, P. E. Scherer, and M. P. Lisanti Caveolin-1 Expression Is Essential for Proper Nonshivering Thermogenesis in Brown Adipose Tissue Diabetes, March 1, 2005; 54(3): 679 - 686. [Abstract] [Full Text] [PDF]

				A. Ost, U. Ortegren, J. Gustavsson, F. H. Nystrom, and P. Stralfors Triacylglycerol Is Synthesized in a Specific Subclass of Caveolae in Primary Adipocytes J. Biol. Chem., January 7, 2005; 280(1): 5 - 8. [Abstract] [Full Text] [PDF]

				T. M. Williams, F. Medina, I. Badano, R. B. Hazan, J. Hutchinson, W. J. Muller, N. G. Chopra, P. E. Scherer, R. G. Pestell, and M. P. Lisanti Caveolin-1 Gene Disruption Promotes Mammary Tumorigenesis and Dramatically Enhances Lung Metastasis in Vivo: ROLE OF CAV-1 IN CELL INVASIVENESS AND MATRIX METALLOPROTEINASE (MMP-2/9) SECRETION J. Biol. Chem., December 3, 2004; 279(49): 51630 - 51646. [Abstract] [Full Text] [PDF]

				D. L. Brasaemle, G. Dolios, L. Shapiro, and R. Wang Proteomic Analysis of Proteins Associated with Lipid Droplets of Basal and Lipolytically Stimulated 3T3-L1 Adipocytes J. Biol. Chem., November 5, 2004; 279(45): 46835 - 46842. [Abstract] [Full Text] [PDF]

				A. W. Cohen, R. Hnasko, W. Schubert, and M. P. Lisanti Role of Caveolae and Caveolins in Health and Disease Physiol Rev, October 1, 2004; 84(4): 1341 - 1379. [Abstract] [Full Text] [PDF]

				S. Collins, W. Cao, and J. Robidoux Learning New Tricks from Old Dogs: {beta}-Adrenergic Receptors Teach New Lessons on Firing Up Adipose Tissue Metabolism Mol. Endocrinol., September 1, 2004; 18(9): 2123 - 2131. [Abstract] [Full Text] [PDF]

				P. Lau, S. J. Nixon, R. G. Parton, and G. E. O. Muscat ROR{alpha} Regulates the Expression of Genes Involved in Lipid Homeostasis in Skeletal Muscle Cells: CAVEOLIN-3 AND CPT-1 ARE DIRECT TARGETS OF ROR J. Biol. Chem., August 27, 2004; 279(35): 36828 - 36840. [Abstract] [Full Text] [PDF]