A new function of the leptin receptor: mediation of the recovery from lipopolysaccharide‐induced hypothermia

• Published in: The FASEB journal 2004-12, Vol.18 (15), p.1949-1951
• Main Authors: Steiner, Alexandre A., Dogan, M. Devrim, Ivanov, Andrei I., Patel, Shreya, Rudaya, Alla Y., Jennings, David H., Orchinik, Miles, Pace, Thaddeus W. W., O’Connor, Kevin A., Watkins, Linda R., Romanovsky, Andrej A.
• Format: Article
• Language: English
• Subjects: Animals; body temperature; Corticosterone - blood; cytokines; Cytokines - biosynthesis; Encephalitis - chemically induced; fever; Fever - chemically induced; Hypothermia - blood; Hypothermia - chemically induced; Hypothermia - immunology; Kinetics; Koletsky rats; Lipopolysaccharides - toxicity; Obesity - complications; Rats; Rats, Mutant Strains; Receptors, Cell Surface - genetics; Receptors, Cell Surface - physiology; Receptors, Leptin; systemic inflammation; tumor necrosis factor corticosterone
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.04-2295fje

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 µg/kg iv) were measured in Koletsky rats exposed to a thermoneutral (28°C) or cool (22°C) environment. Rats of both genotypes responded to LPS with fever at 28°C and with dose‐dependent hypothermia at 22°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‐κB signaling in the hypothalamus and an exaggerated rise in the plasma concentration of tumor necrosis factor (TNF)‐α. 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‐α (80 μg/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‐α, and suppression of inflammatory (via NF‐κB) signaling in the hypothalamus.