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Cited by 586

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

Targeted disruption of hormone-sensitive lipase results in male sterility and adipocyte hypertrophy, but not in obesity

Open access
Osuga, Jun-ichi, Ishibashi, Shun, Oka, Teruaki, Yagyu, Hiroaki, Tozawa, Ryuichi, Fujimoto, Akihisa, Shionoiri, Futoshi, Yahagi, Naoya, Kraemer, Frederic B., Tsutsumi, Osamu, Yamada, Nobuhiro·2000·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.97.2.787
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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.

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Metadata

Authors
Osuga, J.-I., Ishibashi, S., Oka, T., Yagyu, H., Tozawa, R., Fujimoto, A., Shionoiri, F., Yahagi, N., Kraemer, F. B., Tsutsumi, O., & Yamada, N.
Venue
Proceedings of the National Academy of Sciences
Publisher
Proceedings of the National Academy of Sciences
Published
2000-01-18
Volume
97
Issue
2
Pages
787-792
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.97.2.787
OpenAlex
W2121278592
Cited by
586
References
1
FWCI
14.09
Type
journal article
Language
en
Open access
green

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