Human hormone-sensitive lipase (HSL): expression in white fat corrects the white adipose phenotype of HSL-deficient mice.

Abstract

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.

• Authors: Mélanie Fortier, Krishnakant Soni, Nancy Laurin, Shu Pei Wang, Pascale Mauriège, Frank R Jirik, Grant A Mitchell
• Journal: Journal of lipid research (J Lipid Res) Vol. 46 Issue 9 Pg. 1860-7 (Sep 2005) ISSN: 0022-2275 [Print] United States
• PMID: 15961788 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Diglycerides
• Leptin
• Triglycerides
• Sterol Esterase

Topics

• Adipocytes (metabolism)
• Adipose Tissue (chemistry, metabolism)
• Animals
• Diglycerides (analysis)
• Gene Expression
• Genotype
• Humans
• Leptin (blood)
• Lipolysis
• Mice
• Mice, Knockout
• Mice, Transgenic
• Organ Size
• Phenotype
• Sterol Esterase (deficiency, genetics)
• Triglycerides (analysis)