HUSCAP logo Hokkaido Univ. logo

Hokkaido University Collection of Scholarly and Academic Papers >
Graduate School of Medicine / Faculty of Medicine >
Peer-reviewed Journal Articles, etc >

Perilipin promotes hormone-sensitive lipase-mediated adipocyte lipolysis via phosphorylation-dependent and independent mechanisms

Files in This Item:
JBC281-23.pdf680.81 kBPDFView/Open
Please use this identifier to cite or link to this item:http://hdl.handle.net/2115/17252

Title: Perilipin promotes hormone-sensitive lipase-mediated adipocyte lipolysis via phosphorylation-dependent and independent mechanisms
Authors: Miyoshi, Hideaki Browse this author →KAKEN DB
Souza, Sandra C. Browse this author
Zhang, Hui-Hong Browse this author
Strissel, Katherine Browse this author
Christoffolete, Marcelo A Browse this author
Kovsan, Julia Browse this author
Rudich, Assaf Browse this author
Kraemer, Fredric B. Browse this author
Bianco, Antonio C. Browse this author
Martin S., Obin Browse this author
Greenberg, Andrew S. Browse this author
Issue Date: 9-Jun-2006
Publisher: American Society for Biochemistry and Molecular Biology.
Journal Title: Journal of Biological Chemistry
Volume: 281
Issue: 23
Start Page: 15837
End Page: 15844
Publisher DOI: 10.1074/jbc.M601097200
PMID: 16595669
Abstract: Hormone-sensitive lipase (HSL) is the predominant lipase effector of catecholamine-stimulated lipolysis in adipocytes. HSL-dependent lipolysis in response to catecholamines is mediated by protein kinase A (PKA)-dependent phosphorylation of perilipin A (Peri A), an essential lipid droplet (LD)-associated protein. It is believed that perilipin phosphorylation is essential for the translocation of HSL from the cytosol to the LD, a key event in stimulated lipolysis. Using adipocytes retrovirally engineered from murine embryonic fibroblasts of perilipin null mice (Peri–/– MEF), we demonstrate by cell fractionation and confocal microscopy that up to 50% of cellular HSL is LD-associated in the basal state and that PKA-stimulated HSL translocation is fully supported by adenoviral expression of a mutant perilipin lacking all six PKA sites (Peri A1–6). PKA-stimulated HSL translocation was confirmed in differentiated brown adipocytes from perilipin null mice expressing an adipose-specific Peri A1–6 transgene. Thus, PKA-induced HSL translocation was independent of perilipin phosphorylation. However, Peri A1–6 failed to enhance PKA-stimulated lipolysis in either MEF adipocytes or differentiated brown adipocytes. Thus, the lipolytic action(s) of HSL at the LD surface requires PKA-dependent perilipin phosphorylation. In Peri–/– MEF adipocytes, PKA activation significantly enhanced the amount of HSL that could be cross-linked to and co-immunoprecipitated with ectopic Peri A. Notably, this enhanced cross-linking was blunted in Peri–/– MEF adipocytes expressing Peri A1–6. This suggests that PKA-dependent perilipin phosphorylation facilitates (either direct or indirect) perilipin interaction with LD-associated HSL. These results redefine and expand our understanding of how perilipin regulates HSL-mediated lipolysis in adipocytes.
Rights: Copyright © 2006 by the American Society for Biochemistry and Molecular Biology
Type: article (author version)
URI: http://hdl.handle.net/2115/17252
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 三好 秀明

Export metadata:

OAI-PMH ( junii2 , jpcoar )

MathJax is now OFF:


 

 - Hokkaido University