Luminal leptin activates mucin-secreting goblet cells in the large bowel

Am J Physiol Gastrointest Liver Physiol. 2006 Apr;290(4):G805-12. doi: 10.1152/ajpgi.00433.2005. Epub 2006 Feb 2.


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 rat mucin 2 (rMuc2) expression. Wistar rats and ob/ob mice were used. Secretion of mucus was followed in vivo in the rat perfused colon model. Mucus secretion was quantified by ELISA, and rMuc2 mRNA levels were quantified by real-time RT PCR. The effects of leptin alone or in association with protein kinase C (PKC) and phosphatidylinositol 3-kinase (PI3K) inhibitors on mucin secreted by human mucus-secreting HT29-MTX cells were determined. 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 the colonic mucosa. There was no damage to mucosa 24 h after leptin, but the number of stained mucus cells significantly increased. 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 PI3K-dependent pathways. This is the first demonstration that leptin, acting from the luminal side, controls the function of mucus-secreting goblet cells. Because 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.

MeSH terms

  • Animals
  • Cells, Cultured
  • Colon / drug effects
  • Colon / metabolism*
  • Dose-Response Relationship, Drug
  • Enteral Nutrition
  • Goblet Cells / drug effects
  • Goblet Cells / metabolism*
  • HT29 Cells
  • Humans
  • Leptin / administration & dosage*
  • Male
  • Mice
  • Mucins / metabolism*
  • Perfusion
  • Rats
  • Rats, Wistar


  • Leptin
  • Mucins