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

J Clin Invest. 1999 Oct;104(8):1051-9. doi: 10.1172/JCI6762.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Annexin A5 / analysis
  • Apoptosis / drug effects
  • Atrophy
  • Dexamethasone / pharmacology
  • Insulin / blood
  • Leptin / pharmacology*
  • Lymphoid Tissue / pathology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Obese
  • Starvation / pathology*
  • Thymus Gland / pathology*


  • Annexin A5
  • Insulin
  • Leptin
  • Dexamethasone