Leptin induces IL-1 receptor antagonist expression in the brain
Section snippets
Materials and methods
Animals. db/db Mice and their respective lean littermates (C57BL/KsJ) were obtained at seven weeks of age from Central Laboratories for Experimental Animals (Japan). Mice were maintained in a room at 22–24 °C under a constant day–night rhythm and given food and water, ad libitum. All animal experiments were carried out in accordance with NIH Guide for Care and Use of Laboratory Animals and approved by the animal care and use committee at Hokkaido University.
Leptin injection and sample preparation
Effect of leptin on IL-1ra transcripts in the brain
IL-1ra mRNA does not abundantly exist in the brain and it may be difficult to detect without amplification by RT-PCR. Therefore in the present study, RT-PCR analysis was performed to detect cytokine transcript in the brain. We detected basal level of IL-1ra mRNA in the hypothalumus, the hippocampus, the cortex, the cerebellum, and the brain stem (Fig. 1). IL-1ra transcripts were increased 2 h after the application of leptin (5 mg/kg, i.v.) in all of these brain regions tested (Fig. 1).
Time course and dose–response of peripheral leptin on IL-1ra transcripts in the hypothalamus
We next
Discussion
It is well known that effect of leptin in the regulation of appetite and energy expenditure is mediated through hypothalamic center via Ob-Rb receptor (long isoform). Although other isoforms (short isoform of leptin receptor) are expressed in many regions of the brain, their functions have not been elucidated. In the present study, we observed broad expression of leptin-induced IL-1ra transcript throughout the brain even in the region where Ob-Rb receptor is poorly expressed. Using Ob-Rb
Acknowledgements
This research was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports, and Culture, Japan (Y.O., Y.N.), and Research Fellowships of the Japan Society for the Promotion of Science for Young Scientists (T.H.).
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