A new function of the leptin receptor: Mediation of the recovery from lipopolysaccharide-induced hypothermia

Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, United States
The FASEB Journal (Impact Factor: 5.04). 01/2005; 18(15):1949-51. DOI: 10.1096/fj.04-2295fje
Source: PubMed


Obese (f/f) Koletsky rats lack the leptin receptor (LR), whereas their lean (F/?) counterparts bear a fully functional LR. By using f/f and F/? rats, we studied whether the LR is involved in lipopolysaccharide (LPS)-induced fever and hypothermia. The body temperature responses to LPS (10 or 100 microg/kg iv) were measured in Koletsky rats exposed to a thermoneutral (28 degrees C) or cool (22 degrees C) environment. Rats of both genotypes responded to LPS with fever at 28 degrees C and with dose-dependent hypothermia at 22 degrees C. The fever responses of the f/f and F/? rats were identical. The hypothermic response of the f/f rats was markedly prolonged compared with that of the F/? rats. The prolonged hypothermic response to LPS in the f/f rats was accompanied by enhanced NF-kappaB signaling in the hypothalamus and an exaggerated rise in the plasma concentration of tumor necrosis factor (TNF)-alpha. The f/f rats did not respond to LPS with an increase in the plasma concentration of corticosterone or adrenocorticotropic hormone, whereas their F/? counterparts did. The hypothermic response to TNF-alpha (80 microg/kg iv) was markedly prolonged in the f/f rats. These data show that the LR is essential for the recovery from LPS hypothermia. LR-dependent mechanisms of the recovery from LPS hypothermia include activation of the anti-inflammatory hypothalamo-pituitary-adrenal axis, inhibition of both the production and hypothermic action of TNF-alpha, and suppression of inflammatory (via NF-kappaB) signaling in the hypothalamus.

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Available from: Andrei I Ivanov, Apr 10, 2014
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    • "With regard to all aspects and components of the inflammatory sickness syndrome , it is obvious that there are some symptoms which develop briefly after the inflammatory insult whereas the manifestation of other symptoms takes more time to develop. Studies in animals which lack a functional leptin receptor indicate that leptin plays a role in recovery from inflammation-induced hypothermia [19] and sickness behaviour [13]. Both of these responses belong to the later symptoms of systemic inflammation and the time course of their manifestation fits well to the delayed STAT5 signaling in the hypothalamus of leptin-treated rats. "
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