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.