Leptin mediates Clostridium difficile toxin A-induced enteritis in mice

Gastroenterology. 2003 Mar;124(3):683-91. doi: 10.1053/gast.2003.50101.


Background & aims: Leptin regulates energy homeostasis and participates in the regulation of the hypothalamic-pituitary-adrenal axis. Although hyperleptinemia is described in experimental colitis, its role in the pathophysiology of enterotoxin-mediated diarrhea and inflammation remains unclear. We examined the role of leptin in the inflammatory diarrhea induced by toxin A from Clostridium difficile, the causative agent of antibiotic-related colitis.

Methods: Toxin A (10 microg) or buffer were administered in ileal loops of leptin-deficient (ob/ob), leptin-resistant (db/db), or wild-type mice and enterotoxic responses were measured.

Results: In toxin A-treated wild-type mice, circulating leptin and corticosterone levels were increased compared with buffer-injected animals. Toxin A also stimulated increased mucosal expression of the Ob-Rb at the messenger RNA (mRNA) and protein level. Ob/ob and db/db mice were partially protected against toxin A-induced intestinal secretion and inflammation, and this effect was reversed by leptin administration in ob/ob, but not db/db, mice. Basal- and toxin A-stimulated plasma corticosterone levels in ob/ob and db/db mice were higher compared with toxin A-treated wild-type mice. To assess whether the effect of leptin in intestinal inflammation is mediated by corticosteroids we performed adrenalectomy experiments in db/db and wild-type mice. Our results suggested that the diminished intestinal response to toxin A in db/db mice was related only in part to increased levels of corticosteroids.

Conclusions: Leptin plays an important role in regulating the severity of enterotoxin-mediated intestinal secretion and inflammation by activating both corticosteroid-dependent and -independent mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bacterial Toxins*
  • Body Fluids / metabolism
  • Corticosterone / blood
  • Drug Resistance
  • Enteritis / etiology*
  • Enteritis / metabolism
  • Enterotoxins*
  • Leptin / blood
  • Leptin / deficiency
  • Leptin / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Receptors, Cell Surface / metabolism
  • Receptors, Leptin


  • Bacterial Toxins
  • Enterotoxins
  • Leptin
  • Receptors, Cell Surface
  • Receptors, Leptin
  • leptin receptor, mouse
  • tcdA protein, Clostridium difficile
  • Corticosterone