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Fat-specific protein 27 (FSP27) interacts with adipose triglyceride lipase (ATGL) to regulate lipolysis and insulin sensitivity in human adipocytes.

Tan Grahn, Hooi Min LU ; Kaur, Rajween; Yin, Jun; Schweiger, Martina; Sharma, Vishva Mitra; Lee, Mi-Jeong; Ido, Yasuo; Smas, Cynthia M; Zechner, Rudolf and Lass, Achim, et al. (2014) In Journal of Biological Chemistry 289(17). p.12029-12039
Abstract
In adipocytes, lipolysis is a highly regulated process involving hormonal signals, lipid droplet-associated proteins, and lipases. The discovery of new lipid droplet-associated proteins added complexity to the current model of lipolysis. In this study, we used cultured human adipocytes to demonstrate that fat-specific protein 27 (FSP27), an abundantly expressed protein in adipocytes, regulates both basal and stimulated lipolysis by interacting with adipose triglyceride lipase (ATGL, also called desnutrin or PNPLA2). We identified a core domain of FSP27, amino acids 120-220, that interacts with ATGL to inhibit its lipolytic function and promote triglyceride storage. We also defined the role of FSP27 in free fatty acid-induced insulin... (More)
In adipocytes, lipolysis is a highly regulated process involving hormonal signals, lipid droplet-associated proteins, and lipases. The discovery of new lipid droplet-associated proteins added complexity to the current model of lipolysis. In this study, we used cultured human adipocytes to demonstrate that fat-specific protein 27 (FSP27), an abundantly expressed protein in adipocytes, regulates both basal and stimulated lipolysis by interacting with adipose triglyceride lipase (ATGL, also called desnutrin or PNPLA2). We identified a core domain of FSP27, amino acids 120-220, that interacts with ATGL to inhibit its lipolytic function and promote triglyceride storage. We also defined the role of FSP27 in free fatty acid-induced insulin resistance in adipocytes. FSP27 depletion in human adipocytes increased lipolysis and inhibited insulin signaling by decreasing AKT phosphorylation. However, reducing lipolysis by either depletion of ATGL or expression of exogenous full-length FSP27 or amino acids 120-220 protected human adipocytes against the adverse effects of free fatty acids on insulin signaling. In embryonic fibroblasts derived from ATGL KO mice, exogenous free fatty acids did not affect insulin sensitivity. Our results demonstrate a crucial role for FSP27-ATGL interactions in regulating lipolysis, triglyceride accumulation, and insulin signaling in human adipocytes. (Less)
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keywords
Adipocytes: drug effects, Adipocytes: enzymology, Adipocytes: metabolism, Insulin: metabolism, Insulin: pharmacology, Lipase: metabolism, Lipolysis: physiology, Proteins: genetics, Proteins: physiology, Triglycerides: metabolism
in
Journal of Biological Chemistry
volume
289
issue
17
pages
12029 - 12039
publisher
ASBMB
external identifiers
  • pmid:24627478
  • scopus:84899428316
ISSN
1083-351X
DOI
10.1074/jbc.M113.539890
language
English
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no
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305af226-65c3-410c-a029-a80cd522cbfb (old id 5425013)
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http://www.ncbi.nlm.nih.gov/pubmed/24627478?dopt=Abstract
date added to LUP
2015-05-21 07:37:37
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2017-10-22 03:12:06
@article{305af226-65c3-410c-a029-a80cd522cbfb,
  abstract     = {In adipocytes, lipolysis is a highly regulated process involving hormonal signals, lipid droplet-associated proteins, and lipases. The discovery of new lipid droplet-associated proteins added complexity to the current model of lipolysis. In this study, we used cultured human adipocytes to demonstrate that fat-specific protein 27 (FSP27), an abundantly expressed protein in adipocytes, regulates both basal and stimulated lipolysis by interacting with adipose triglyceride lipase (ATGL, also called desnutrin or PNPLA2). We identified a core domain of FSP27, amino acids 120-220, that interacts with ATGL to inhibit its lipolytic function and promote triglyceride storage. We also defined the role of FSP27 in free fatty acid-induced insulin resistance in adipocytes. FSP27 depletion in human adipocytes increased lipolysis and inhibited insulin signaling by decreasing AKT phosphorylation. However, reducing lipolysis by either depletion of ATGL or expression of exogenous full-length FSP27 or amino acids 120-220 protected human adipocytes against the adverse effects of free fatty acids on insulin signaling. In embryonic fibroblasts derived from ATGL KO mice, exogenous free fatty acids did not affect insulin sensitivity. Our results demonstrate a crucial role for FSP27-ATGL interactions in regulating lipolysis, triglyceride accumulation, and insulin signaling in human adipocytes.},
  author       = {Tan Grahn, Hooi Min and Kaur, Rajween and Yin, Jun and Schweiger, Martina and Sharma, Vishva Mitra and Lee, Mi-Jeong and Ido, Yasuo and Smas, Cynthia M and Zechner, Rudolf and Lass, Achim and Puri, Vishwajeet},
  issn         = {1083-351X},
  keyword      = {Adipocytes: drug effects,Adipocytes: enzymology,Adipocytes: metabolism,Insulin: metabolism,Insulin: pharmacology,Lipase: metabolism,Lipolysis: physiology,Proteins: genetics,Proteins: physiology,Triglycerides: metabolism},
  language     = {eng},
  number       = {17},
  pages        = {12029--12039},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Fat-specific protein 27 (FSP27) interacts with adipose triglyceride lipase (ATGL) to regulate lipolysis and insulin sensitivity in human adipocytes.},
  url          = {http://dx.doi.org/10.1074/jbc.M113.539890},
  volume       = {289},
  year         = {2014},
}