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1 INSERM, Unite 45, Lyon, France; Universite Claude Bernard, UCLB-Lyon1, Faculte de Medecine R. Laennec, IFR62, Llyon, France; INRA Laboratoire d'Ecologie et de Physiologie du Systeme Digestif, INRA, Jouy-en -Josas, France
2 INSERM, Unite 683, Paris, France; Universite Paris 7, Faculte de Medeine Xavier Bichat, IFR 02, Paris, France
3 INSERM, Unite 45, Lyon, France; Universite Claude Bernard, UCLB-Lyon1, Faculte de Medecine R. Laennec, IFR62, Llyon, France
4 Universite Paris 7, Faculte de Medeine Xavier Bichat, IFR 02, Paris, France
* To whom correspondence should be addressed. E-mail: bado{at}bichat.inserm.fr.
Background and Aim: Leptin has been suggested to be involved in tissue injury and/or mucosal defence mechanisms. Here we studied the effects of leptin on colonic mucus secretion and on rMuc2 mucin expression. Methods: Wistar rats and ob/ob mice were used. Secretion of mucus was followed in vivo in rat perfused colon model. Mucus secretion was quantified by ELISA and rMuc2 mRNA levels by real time RT PCR. The effects of leptin alone or in association with PKC and PI3 kinase inhibitors, on mucin secreted by the human mucus-secreting HT29-MTX cells, were determined. Results: Leptin was detected in the rat colonic lumen at substantial levels. Luminal perfusion of leptin stimulates mucus-secreting goblet cells in a dose-dependent manner in vivo in the rat. Leptin (10 nmol/L) increased mucus secretion by a factor of 3.5 and doubled rMuc2 mRNA levels in colonic mucosa. There was no damage to mucosa 24 hours after leptin, but the number of stained mucus cells had significantly increased. The leptin-deficient ob/ob mice have abnormally dense mucus-filled goblet cells. In human colonic goblet-like HT29-MTX cells expressing leptin receptors, leptin increased mucin secretion by activating PKC and PI3 kinase-dependent pathways. Conclusion: This is the first demonstration that leptin, acting from the luminal side, controls the function of the mucus-secreting goblet cells. As the gel layer formed by mucus at the surface of the intestinal epithelium has a barrier function, our data may be relevant physiologically in defence mechanisms of the gastrointestinal tract.
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