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Adipocyte lipases and defect of lipolysis in human obesity

Langin, D; Dicker, A; Tavernier, G; Hoffstedt, J; Mairal, A; Ryden, M; Arner, E; Sicard, A; Jenkins, C M and Viguerie, N, et al. (2005) In Diabetes 54(11). p.3190-3197
Abstract
The mobilization of fat stored in adipose tissue is mediated by hormone-sensitive lipase (HSL) and the recently characterized adipose triglyceride lipase (ATGL), yet their relative importance in lipolysis is unknown. We show that a novel potent inhibitor of HSL does not inhibit other lipases. The compound counteracted catecholamine-stimulated lipolysis in mouse adipocytes and had no effect on residual triglyceride hydrolysis and lipolysis in HSL-null mice. In human adipocytes, catecholamine- and natriuretic peptide-induced lipolysis were completely blunted by the HSL inhibitor. When fat cells were not stimulated, glycerol but not fatty acid release was inhibited. HSL and ATGL mRNA levels increased concomitantly during adipocyte... (More)
The mobilization of fat stored in adipose tissue is mediated by hormone-sensitive lipase (HSL) and the recently characterized adipose triglyceride lipase (ATGL), yet their relative importance in lipolysis is unknown. We show that a novel potent inhibitor of HSL does not inhibit other lipases. The compound counteracted catecholamine-stimulated lipolysis in mouse adipocytes and had no effect on residual triglyceride hydrolysis and lipolysis in HSL-null mice. In human adipocytes, catecholamine- and natriuretic peptide-induced lipolysis were completely blunted by the HSL inhibitor. When fat cells were not stimulated, glycerol but not fatty acid release was inhibited. HSL and ATGL mRNA levels increased concomitantly during adipocyte differentiation. Abundance of the two transcripts in human adipose tissue was highly correlated in habitual dietary conditions and during a hypocaloric diet, suggesting common regulatory mechanisms for the two genes. Comparison of obese and nonobese subjects showed that obesity was associated with a decrease in catecholamine-induced lipolysis and HSL expression in mature fat cells and in differentiated preadipocytes. In conclusion, HSL is the major lipase for catecholamine- and natriuretic peptide-stimulated lipolysis, whereas ATGL mediates the hydrolysis of triglycerides during basal lipolysis. Decreased catecholamine-induced lipolysis and low HSL expression constitute a possibly primary defect in obesity. (Less)
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Contribution to journal
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published
subject
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Diabetes
volume
54
issue
11
pages
3190 - 3197
publisher
American Diabetes Association Inc.
external identifiers
  • pmid:16249444
  • wos:000233023100018
  • scopus:30744477567
ISSN
1939-327X
language
English
LU publication?
yes
id
f207ea0a-e37c-4ac5-b856-9bb973549cc3 (old id 213958)
alternative location
http://diabetes.diabetesjournals.org/cgi/reprint/54/11/3190
date added to LUP
2007-08-03 12:10:48
date last changed
2017-11-19 04:03:18
@article{f207ea0a-e37c-4ac5-b856-9bb973549cc3,
  abstract     = {The mobilization of fat stored in adipose tissue is mediated by hormone-sensitive lipase (HSL) and the recently characterized adipose triglyceride lipase (ATGL), yet their relative importance in lipolysis is unknown. We show that a novel potent inhibitor of HSL does not inhibit other lipases. The compound counteracted catecholamine-stimulated lipolysis in mouse adipocytes and had no effect on residual triglyceride hydrolysis and lipolysis in HSL-null mice. In human adipocytes, catecholamine- and natriuretic peptide-induced lipolysis were completely blunted by the HSL inhibitor. When fat cells were not stimulated, glycerol but not fatty acid release was inhibited. HSL and ATGL mRNA levels increased concomitantly during adipocyte differentiation. Abundance of the two transcripts in human adipose tissue was highly correlated in habitual dietary conditions and during a hypocaloric diet, suggesting common regulatory mechanisms for the two genes. Comparison of obese and nonobese subjects showed that obesity was associated with a decrease in catecholamine-induced lipolysis and HSL expression in mature fat cells and in differentiated preadipocytes. In conclusion, HSL is the major lipase for catecholamine- and natriuretic peptide-stimulated lipolysis, whereas ATGL mediates the hydrolysis of triglycerides during basal lipolysis. Decreased catecholamine-induced lipolysis and low HSL expression constitute a possibly primary defect in obesity.},
  author       = {Langin, D and Dicker, A and Tavernier, G and Hoffstedt, J and Mairal, A and Ryden, M and Arner, E and Sicard, A and Jenkins, C M and Viguerie, N and van Harmelen, V and Gross, R W and Holm, Cecilia and Arner, P},
  issn         = {1939-327X},
  language     = {eng},
  number       = {11},
  pages        = {3190--3197},
  publisher    = {American Diabetes Association Inc.},
  series       = {Diabetes},
  title        = {Adipocyte lipases and defect of lipolysis in human obesity},
  volume       = {54},
  year         = {2005},
}