Hyperleptinemia and reduced TNF-α secretion cause resistance of db/db mice to endotoxin

Abram M. Madiehe, Tiffany D. Mitchell, Ruth Babette Harris

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

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 db3J / db3J (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-α in fed and fasted BL/3J and BL/6J mice. TNF-α was increased three- and fourfold in BL/3J and BL/6J, respectively. LPS (100 μg) 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 μg leptin prevented the drop in rectal temperature, blunted the increase in corticosterone, but had no effect on TNF-α induced by 100 μg 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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume284
Issue number3 53-3
StatePublished - Mar 1 2003
Externally publishedYes

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Endotoxins
Leptin Receptors
Leptin
Corticosterone
Cytokine Receptors
Temperature
Mortality
Septic Shock
Intraperitoneal Injections
Protein Isoforms

Keywords

  • Leptin receptor
  • Lipopolysaccharides
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Hyperleptinemia and reduced TNF-α secretion cause resistance of db/db mice to endotoxin. / Madiehe, Abram M.; Mitchell, Tiffany D.; Harris, Ruth Babette.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 284, No. 3 53-3, 01.03.2003.

Research output: Contribution to journalArticle

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