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

Jane K. Howard, Graham M. Lord, Giuseppe Matarese, Silvia Vendetti, Mohammad A. Ghatei, Mary A. Ritter, Robert I. Lechler, Stephen R. Bloom

Research output: Contribution to journalArticle

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 apoprosis 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.

Original languageEnglish
Pages (from-to)1051-1059
Number of pages9
JournalJournal of Clinical Investigation
Volume104
Issue number8
Publication statusPublished - Oct 1999

ASJC Scopus subject areas

  • Medicine(all)

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