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Cited by 567

The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.

Leptin protects mice from starvation-induced lymphoid atrophy and increases thymic cellularity in ob/ob mice

Open access
Howard, Jane K., Lord, Graham M., Matarese, Giuseppe, Vendetti, Silvia, Ghatei, Mohammad A., Ritter, Mary A., Lechler, Robert I., Bloom, Stephen R.·1999·Journal of Clinical Investigation

Abstract

Thymic atrophy is a prominent feature of malnutrition. Forty-eight hours' starvation of normal mice reduced the total thymocyte count to 13% of that observed in freely fed controls, predominantly because of a diminution in the cortical CD4(+)CD8(+) thymocyte subpopulation. Prevention of the fasting-induced fall in the level of the adipocyte-derived hormone leptin by administering exogenous recombinant leptin protected mice from these starvation-induced thymic changes. The ob/ob mouse, which is unable to produce functional leptin because of a mutation in the obese gene, has impaired cellular immunity together with a marked reduction in the size and cellularity of the thymus. We found that ob/ob mice had a high level of thymocyte apoptosis resulting in a ratio of CD4(+)CD8(+) (cortical) to CD4(-)CD8(-) (precursor) thymocytes that was 4-fold lower than that observed in wild-type mice. Peripheral administration of recombinant leptin to ob/ob mice reduced thymocyte apoptosis and substantially increased both thymic cellularity and the CD4(+)CD8(+)/CD4(-)CD8(-) ratio. In contrast, a comparable weight loss in pair-fed PBS-treated ob/ob mice had no impact on thymocyte number. In vitro, leptin protected thymocytes from dexamethasone-induced apoptosis. These data indicate that reduced circulating leptin concentrations are pivotal in the pathogenesis of starvation-induced lymphoid atrophy.

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Crossref · 10.1172/jci6762

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Metadata

Authors
Howard, J. K., Lord, G. M., Matarese, G., Vendetti, S., Ghatei, M. A., Ritter, M. A., Lechler, R. I., & Bloom, S. R.
Venue
Journal of Clinical Investigation
Published
1999-10-15
Volume
104
Issue
8
Pages
1051-1059
ISSN
0021-9738 (ISSN-L)
OpenAlex
W2165345254
Cited by
567
References
6
FWCI
6.20
Type
journal article
Language
en
Open access
green

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