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

JK Howard, GM Lord, G Matarese… - The Journal of …, 1999 - Am Soc Clin Investig
JK Howard, GM Lord, G Matarese, S Vendetti, MA Ghatei, MA Ritter, RI Lechler, SR Bloom
The Journal of clinical investigation, 1999Am Soc Clin Investig
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 …
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 CD4CD8 (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+/CD4CD8 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.
The Journal of Clinical Investigation