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

• Miyoshi, Hideaki

• Souza, Sandra C.

• Zhang, Hui-Hong

• Strissel, Katherine

• Christoffolete, Marcelo A

• Kovsan, Julia

• Rudich, Assaf

• Kraemer, Fredric B.

• Bianco, Antonio C.

• Martin S., Obin

• Greenberg, Andrew S.

抄録

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.

収録刊行物

• Journal of Biological Chemistry

  Journal of Biological Chemistry 281 (23), 15837-15844, 2006-06-09

  American Society for Biochemistry and Molecular Biology.

詳細情報

• CRID: 1050845763912501248
• NII論文ID: 120000970417
• ISSN: 1083351X
• ISSN: 00219258
• HANDLE: 2115/17252
• 本文言語コード: en
• 資料種別: journal article
• データソース種別:
  • IRDB
  • CiNii Articles