| First Author | Fortier M | Year | 2005 |
| Journal | J Lipid Res | Volume | 46 |
| Issue | 9 | Pages | 1860-7 |
| PubMed ID | 15961788 | Mgi Jnum | J:100480 |
| Mgi Id | MGI:3588614 | Doi | 10.1194/jlr.M500081-JLR200 |
| Citation | Fortier M, et al. (2005) Human hormone-sensitive lipase (HSL): expression in white fat corrects the white adipose phenotype of HSL-deficient mice. J Lipid Res 46(9):1860-7 |
| abstractText | In white adipose tissue (WAT), hormone-sensitive lipase (HSL) can mediate lipolysis, a central pathway in obesity and diabetes. Gene-targeted HSL-deficient (HSL(-/-)) mice with no detectable HSL peptide or activity (measured as cholesteryl esterase) have WAT abnormalities, including low mass, marked heterogeneity of cell diameter, increased diacylglycerol content, and low beta-adrenergic stimulation of adipocyte lipolysis. Three transgenic mouse strains preferentially expressing human HSL in WAT were bred to a HSL(-/-) background. One, HSL(-/-)N, expresses normal human HSL (41.3 +/- 9.1% of normal activity); two express a serine-to-alanine mutant (S554A) initially hypothesized to be constitutively active: HSL(-/-)ML, 50.3 +/- 12.3% of normal, and HSL(-/-)MH, 69.8 +/- 15.8% of normal. In WAT, HSL(-/-)N mice resembled HSL(+/+) controls in WAT mass, histology, diacylglyceride content, and lipolytic response to beta-adrenergic agents. In contrast, HSL(-/-) ML and HSL(-/-)MH mice resembled nontransgenic HSL(-/-) mice, except that diacylglycerol content and perirenal and inguinal WAT masses approached normal in HSL(-/-)MH mice. Therefore, 1) WAT expression of normal human HSL markedly improves HSL(-/-) WAT biochemically, physiologically, and morphologically; 2) similar levels of S554A HSL have a low physiological effect despite being active in vitro; and 3) diacylglycerol accumulation is not essential for the development of the characteristic WAT pathology of HSL(-/-) mice. |
