| 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)
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