Leptin induces IL-1 receptor antagonist expression in the brain

doi:10.1016/S0006-291X(02)00486-2

Biochemical and Biophysical Research Communications

Volume 294, Issue 2, 7 June 2002, Pages 215-219

https://doi.org/10.1016/S0006-291X(02)00486-2 Get rights and content

Abstract

The ob gene product, leptin, is known to be an important circulating signal for regulation of food intake and body weight. We report here that peripherally applied leptin increased interleukin-1 receptor antagonist (IL-1ra) transcripts in the hypothalamus. Interestingly, we observed leptin-induced increase in IL-1ra transcripts not only in the hypothalamus but also in other brain regions such as the hippocampus, the cortex, the cerebellum, and the brain stem. Moreover, leptin applied to the db/db mice, which lack functional Ob-Rb receptor, increased IL-1ra mRNA levels in the hyothalamus to a similar extent as in normal mice. These results indicate that the leptin-induced IL-1ra expression in the brain may be mediated through STAT3 independent mechanisms.

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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Leptin induces IL-1 receptor antagonist expression in the brain

Abstract

Section snippets

Materials and methods

Effect of leptin on IL-1ra transcripts in the brain

Time course and dose–response of peripheral leptin on IL-1ra transcripts in the hypothalamus

Discussion

Acknowledgements

Biochem. Biophys. Res. Commun.

Cell

Mol. Cell Endocrinol.

FEBS Lett.

FEBS Lett.

J. Biol. Chem.

J. Biol. Chem.

Biochem. Biophys. Res. Commun.

J. Biol. Chem.

Am. J. Pathol.

Positional cloning of the mouse obese gene and its human homologue

Nature

IL-1β mediates leptin induction during inflammation

Am. J. Physiol.

Leptin regulates proinflammatory immune responses

FASEB J.

Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression

Nature

Leptin actions on food intake and body temperature are mediated by IL-1

Proc. Natl. Acad. Sci. USA