Human hormone-sensitive lipase (HSL): expression in white fat corrects the white adipose phenotype of HSL-deficient mice
Copyright policy )Human hormone-sensitive lipase (HSL): expression in white fat corrects the white adipose phenotype of HSL-deficient mice
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.
- Université Laval Canada
- University of Calgary Canada
Leptin, Genotype, Lipolysis, Gene Expression, Mice, Transgenic, QD415-436, adipocyte, Biochemistry, Diglycerides, Mice, Adipocytes, Animals, Humans, mouse, Triglycerides, Mice, Knockout, fat metabolism, Organ Size, Sterol Esterase, Phenotype, hormone-sensitive lipase, Adipose Tissue, mutation
Leptin, Genotype, Lipolysis, Gene Expression, Mice, Transgenic, QD415-436, adipocyte, Biochemistry, Diglycerides, Mice, Adipocytes, Animals, Humans, mouse, Triglycerides, Mice, Knockout, fat metabolism, Organ Size, Sterol Esterase, Phenotype, hormone-sensitive lipase, Adipose Tissue, mutation
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