Targeted disruption of hormone-sensitive lipase results in male sterility and adipocyte hypertrophy, but not in obesity
Jun-ichi Osuga,Shun Ishibashi,Teruaki Oka,Hiroaki Yagyu,Ryu-ichi Tozawa,Akihisa Fujimoto,Futoshi Shionoiri,Naoya Yahagi,Frederic B. Kraemer,Osamu Tsutsumi,Nobuhiro Yamada +10 more
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It is shown that HSL is required for spermatogenesis but is not the only enzyme that mediates the hydrolysis of triacylglycerol stored in adipocytes, and that adipocytes were significantly enlarged and the size differences between cell and tissue suggests the heterogeneity of adipocytes.Abstract:
Hormone-sensitive lipase (HSL) is known to mediate the hydrolysis not only of triacylglycerol stored in adipose tissue but also of cholesterol esters in the adrenals, ovaries, testes, and macrophages. To elucidate its precise role in the development of obesity and steroidogenesis, we generated HSL knockout mice by homologous recombination in embryonic stem cells. Mice homozygous for the mutant HSL allele (HSL−/−) were superficially normal except that the males were sterile because of oligospermia. HSL−/− mice did not have hypogonadism or adrenal insufficiency. Instead, the testes completely lacked neutral cholesterol ester hydrolase (NCEH) activities and contained increased amounts of cholesterol ester. Many epithelial cells in the seminiferous tubules were vacuolated. NCEH activities were completely absent from both brown adipose tissue (BAT) and white adipose tissue (WAT) in HSL−/− mice. Consistently, adipocytes were significantly enlarged in the BAT (5-fold) and, to a lesser extent in the WAT (2-fold), supporting the concept that the hydrolysis of triacylglycerol was, at least in part, impaired in HSL−/− mice. The BAT mass was increased by 1.65-fold, but the WAT mass remained unchanged. Discrepancy of the size differences between cell and tissue suggests the heterogeneity of adipocytes. Despite these morphological changes, HSL−/− mice were neither obese nor cold sensitive. Furthermore, WAT from HSL−/− mice retained 40% of triacylglycerol lipase activities compared with the wild-type WAT. In conclusion, HSL is required for spermatogenesis but is not the only enzyme that mediates the hydrolysis of triacylglycerol stored in adipocytes.read more
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Le tissu adipeux : nouveaux aspects
TL;DR: La creation of modeles de souris transgeniques dont certains presentent un phenotype resistant a l’obesite, permet d’identifier de nouvelles cibles adipocytaires pour le traitement de l”obesites”.
Molecular Mechanisms of Glucolipotoxicity in Diabetes
Malin Fex,Hindrik Mulder +1 more
TL;DR: It is found that HSL (hormone-sensitive lipase), the rate-limiting enzyme for acylglycerol hydrolysis in adipocytes, is expressed in rodent β-cells and this role is resolved, demonstrating that lipases, such as HSL, play a regulatory role in β-cell stimulus– secretion coupling.
rats and increases protein levels of class B scavenger receptors
Lobo Mvt,María I. Arenas,Lydia Huerta,S. Sacristán,Miriam Pérez-Crespo,Alfonso Gutiérrez-Adán,Díaz Gil Jj +6 more
TL;DR: The observed effects of LGF would facilitate the provision of cholesterol for sperm cell growth and Leydig cell recovery and it is suggested that the pivotal role of SR-BI in the uptake of cholesteryl esters from HDL.
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Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese
Sven Enerbäck,Anders Jacobsson,Elizabeth M. Simpson,Carmen Guerra,Hitoshi Yamashita,Mary-Ellen Harper,Leslie P. Kozak +6 more
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