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Gastroenterology. 2003 Mar;124(3):683-91.

Leptin mediates Clostridium difficile toxin A-induced enteritis in mice.

Author information

1
Divisions of Gastroenterology and Endocrinology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.

Abstract

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.

PMID:
12612907
DOI:
10.1053/gast.2003.50101
[Indexed for MEDLINE]

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