Role of central Leptin signaling in the starvation-induced alteration of B-cell development

Miyako Tanaka, Takayoshi Suganami, Misa Kim-Saijo, Chitoku Toda, Makoto Tsuiji, Kozue Ochi, Yasutomi Kamei, Yasuhiko Minokoshi, Yoshihiro Ogawa

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37 Citations (Scopus)

Abstract

Nutritional deprivation or malnutrition suppresses immune function in humans and animals, thereby conferring higher susceptibility to infectious diseases. Indeed, nutritional deprivation induces atrophy of lymphoid tissues such as thymus and spleen and decreases the number of circulating lymphocytes. Leptin, a major adipocytokine, is exclusively produced in the adipose tissue in response to the nutritional status and acts on the hypothalamus, thereby regulating energy homeostasis. Although leptin plays a critical role in the starvation-induced T-cell-mediated immunosuppression, little is known about its role in B-cell homeostasis under starvation conditions. Here we show the alteration of B-cell development in the bone marrow of fasted mice, characterized by decrease in pro-B, pre-B, and immature B cells and increase in mature B cells. Interestingly, intracerebroventricular leptin injection was sufficient to prevent the alteration of B-cell development of fasted mice. The alteration of B lineage cells in the bone marrow of fasted mice was markedly prevented by oral administration of glucocorticoid receptor antagonist RU486 (11β-[p-(dimethylamino)phenyl]-17β-hydroxy-17-(1-propynyl)estra-4,9-dien-3-one). It was also effectively prevented by intracerebroventricular injection of neuropeptide Y Y1 receptor antagonist BIBP3226 [(2R)-5-(diaminomethylideneamino)-2-[(2,2-diphenylacetyl)amino]-N-[(4-hydroxyphenyl)methyl]pentanamide], along with suppression of the otherwise increased serum corticosterone concentrations. This study provides the first in vivo evidence for the role of central leptin signaling in the starvation-induced alteration of B-cell development. The data of this study suggest that the CNS, which is inherent to integrate information from throughout the organism, is able to control immune function.

Original languageEnglish
Pages (from-to)8373-8380
Number of pages8
JournalJournal of Neuroscience
Volume31
Issue number23
DOIs
Publication statusPublished - Jun 8 2011

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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    Tanaka, M., Suganami, T., Kim-Saijo, M., Toda, C., Tsuiji, M., Ochi, K., Kamei, Y., Minokoshi, Y., & Ogawa, Y. (2011). Role of central Leptin signaling in the starvation-induced alteration of B-cell development. Journal of Neuroscience, 31(23), 8373-8380. https://doi.org/10.1523/JNEUROSCI.6562-10.2011