Leptin: a new growth factor for the small intestine.

PURPOSE

This study was designed to evaluate the potential growth factor effects of systemic administration of leptin on mucosal mass and absorptive function in normal rat intestine.

METHODS

Twenty male Sprague-Dawley rats underwent placement of a jugular venous catheter connected to a subcutaneous osmotic pump designed to deliver its contents at a constant rate. The rats were divided into 4 groups (n = 5 per group) based on the contents of the osmotic pump: group 1, 0.1% bovine serum albumin; group 2, leptin, 6.25 microgram/kg/d; Group 3, leptin, 18.75 microgram/kg/d; Group 4, leptin, 43.75 microgram/kg/d. After a 14-day infusion, [(14)C] galactose and [(14)C] glycine absorption were determined using a closed, recirculation technique. DNA content was determined from mucosal biopsies. Total RNA was extracted from mucosal samples, reverse transcribed, and amplified via polymerase chain reaction for the following primer pairs: sodium/glucose cotransporter (SGLT-1), fructose transporter (GLUT-5), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH, internal standard). Statistical analysis was performed by analysis of variance and expressed as mean plus minus SEM.

RESULTS

Systemic administration of increasing doses of leptin enhanced DNA content when compared with the appropriate control (group 2, 1.06 plus minus 0.04 [P <.05]; group 3, 1.1 plus minus 0.05 [P <.01]; and group 4, 1.07 plus minus 0.06 [P <.05]. Leptin enhanced mucosal absorptive function (galactose: group 2, 2.31 plus minus 0.15 [P <.01]; group 3, 2.71 plus minus 0.06 [P <.01]; group 4, 2.19 plus minus 0.28 [P <.05]; glycine: group 2, 2.34 plus minus 0.31 [P <.05]; group 3, 3.32 plus minus 0.14 [P <.01]; group 4, 3.1 plus minus 0.27 [P <.01]) in the normal intestine when compared with the appropriate control animals. Also, leptin enhanced the gene expression of the carbohydrate transporters when compared with the appropriate control rats.

CONCLUSIONS

These data show that systemic leptin administration enhances mucosal mass and absorptive function in normal rat intestine. Thus, leptin appears to be a growth factor for normal small intestine and may play a role in patients who acquire intestinal dysfunction.