RT Journal Article
SR Electronic
T1 Adipocyte Lipases and Defect of Lipolysis in Human Obesity
JF Diabetes
JO Diabetes
FD American Diabetes Association
SP 3190
OP 3197
DO 10.2337/diabetes.54.11.3190
VO 54
IS 11
A1 Langin, Dominique
A1 Dicker, Andrea
A1 Tavernier, Geneviève
A1 Hoffstedt, Johan
A1 Mairal, Aline
A1 Rydén, Mikael
A1 Arner, Erik
A1 Sicard, Audrey
A1 Jenkins, Christopher M.
A1 Viguerie, Nathalie
A1 van Harmelen, Vanessa
A1 Gross, Richard W.
A1 Holm, Cecilia
A1 Arner, Peter
YR 2005
UL http://diabetes.diabetesjournals.org/content/54/11/3190.abstract
AB 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.