マウスリンパ組織におけるレプチンレセプターの発現

The mammalian thymus involutes with age. Both the decrease of lymphocyte-accumulated region and the replacement by fat tissue begin at puberty and continue throughout life. In the mouse thymus, though no typical fat cells are found at birth, fat cells appeared at the latest 3 weeks old preceding to the atrophy of cortical and medullary regions. Physiological functions of fat cells proliferated and differentiated in the thymus after birth are unknown. As fat cells appeared in the 3-week-old mouse thymus have shown to express leptin mRNA, we examined whether leptin receptor type b (OBRL) is expressed or not in the thymus and, in comparison, in the secondary lymphoid tissues, spleen, mesenteric lymph node and Peyer' s patch. OBRL mRNA was detected in both thymus and all secondary lymphoid tissues examined by RTPCR method. Furthermore, OBRL mRNA was also detected in the isolated cells with mouse-lymphocyte separation medium from both thymus and spleen free cells washed out in saline from dissected tissues. It is suggested that fat cells differenciated as early as 3 weeks old in the thymus produce leptin and affect other thymus cells, lymphocytes probably, through OBRL. It remains to be clarified whether the leptin-OBRL interaction influences age involution in the thymus

Brain fractalkine-CX3CR1 signalling is anti-obesity system as anorexigenic and anti-inflammatory actions in diet-induced obese mice

Abstract Fractalkine is one of the CX3C chemokine family, and it is widely expressed in the brain including the hypothalamus. In the brain, fractalkine is expressed in neurons and binds to a CX3C chemokine receptor 1 (CX3CR1) in microglia. The hypothalamus regulates energy homeostasis of which dysregulation is associated with obesity. Therefore, we examined whether fractalkine-CX3CR1 signalling involved in regulating food intake and hypothalamic inflammation associated with obesity pathogenesis. In the present study, fractalkine significantly reduced food intake induced by several experimental stimuli and significantly increased brain-derived neurotrophic factor (BDNF) mRNA expression in the hypothalamus. Moreover, tyrosine receptor kinase B (TrkB) antagonist impaired fractalkine-induced anorexigenic actions. In addition, compared with wild-type mice, CX3CR1-deficient mice showed a significant increase in food intake and a significant decrease in BDNF mRNA expression in the hypothalamus. Mice fed a high-fat diet (HFD) for 16 weeks showed hypothalamic inflammation and reduced fractalkine mRNA expression in the hypothalamus. Intracerebroventricular administration of fractalkine significantly suppressed HFD-induced hypothalamic inflammation in mice. HFD intake for 4 weeks caused hypothalamic inflammation in CX3CR1-deficient mice, but not in wild-type mice. These findings suggest that fractalkine-CX3CR1 signalling induces anorexigenic actions via activation of the BDNF-TrkB pathway and suppresses HFD-induced hypothalamic inflammation in mice