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J. Biol. Chem., Vol. 280, Issue 52, 43109-43120, December 30, 2005
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Perilipin Targets a Novel Pool of Lipid Droplets for Lipolytic Attack by Hormone-sensitive Lipase*
From the
||Center for Integrative Metabolic and Endocrine Research, the Department of Psychiatry and Behavioral Neurosciences and the ¶Department of Pharmacology, Physiology, Radiology, and Biomedical Engineering, Wayne State University School of Medicine, Detroit, Michigan 48201, the Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, the College of Arts and Sciences, Lawrence Technological University, Southfield, Michigan 48075, and the **Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota 55455
Adipocytes serve as the principal energy reservoir of the body; however, the subcellular organization of the machinery regulating lipid trafficking and metabolism is poorly understood. Mobilization of stored triglyceride is thought be controlled by interactions among intracellular lipases and proteins that coat lipid storage droplets. A major limitation of previous studies of hormone-mediated lipolysis, however, is the use of cultured model adipocytes whose three-dimensional architectures do not resemble those in real adipose tissue. To address this limitation, we investigated the intracellular targeting of perilipin, a major lipid coat protein, and hormone-sensitive lipase in three preparations that exhibit more appropriate morphologies: 3T3-L1 adipocytes grown in three-dimensional matrix, dissociated mature adipocytes from mouse adipose tissue, and adipocytes within intact fat pads. High resolution imaging of native and fluorescently tagged proteins indicate that: 1) perilipin preferentially targets a special class of peripheral lipid storage droplets, but not the major or central lipid storage droplets, 2) the peripheral droplets are the sites of attack by hormone-sensitive lipase, and 3) perilipin and hormone-sensitive lipase are continuously colocalized following lipolytic activation. These results indicate that in white adipose tissue, lipolysis takes place in a specialized subcellular domain that is distinct from the major lipid storage site and is defined by perilipin.
Received for publication, June 10, 2005 , and in revised form, October 12, 2005.
* This work was supported by National Institutes of Health Grants DK 062292 and DK 066505 (to J. G. G.), R24RR14891 (to H.-P. H. M.), and DK 053189 (to D. A. B.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1-S5.
1 To whom correspondence should be addressed: Dept. of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, 550 E. Canfield, Detroit, MI 48201. Tel.: 313-577-5629; Fax: 313-577-9469; E-mail: jgranne{at}med.wayne.edu.
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