| First Author | Madiehe AM | Year | 2003 |
| Journal | Am J Physiol Regul Integr Comp Physiol | Volume | 284 |
| Issue | 3 | Pages | R763-70 |
| PubMed ID | 12571077 | Mgi Jnum | J:82497 |
| Mgi Id | MGI:2653412 | Doi | 10.1152/ajpregu.00610.2002 |
| Citation | Madiehe AM, et al. (2003) Hyperleptinemia and reduced TNF-alpha secretion cause resistance of db/db mice to endotoxin. Am J Physiol Regul Integr Comp Physiol 284(3):R763-70 |
| abstractText | Leptin deficiency in ob/ob mice increases susceptibility to endotoxic shock, whereas leptin pretreatment protects them against LPS-induced lethality. Lack of the long-form leptin receptor (Ob-Rb) in db/db mice causes resistance. We tested the effects of LPS in C57BL/6J db(3J)/db(3J) (BL/3J) mice, which express only the circulating leptin receptors, compared with C57BL/6J db/db (BL/6J) mice, which express all short-form and circulating isoforms of the leptin receptor. Intraperitoneal injections of LPS significantly decreased rectal temperature and increased leptin, corticosterone, and free TNF-alpha in fed and fasted BL/3J and BL/6J mice. TNF-alpha was increased three- and fourfold in BL/3J and BL/6J, respectively. LPS (100 microg) caused 50% mortality of fasted BL/6J mice but caused no mortality in fasted BL/3J mice. Pretreatment of fasted BL/3J mice with 30 microg leptin prevented the drop in rectal temperature, blunted the increase in corticosterone, but had no effect on TNF-alpha induced by 100 microg LPS. Taken together, these data provide evidence that fasted BL/3J mice are more resistant than BL/6J mice to LPS toxicity, presumably due to the absence of leptin receptors in BL/3J mice. This resistance may be due to high levels of free leptin cross-reacting with other cytokine receptors. |
