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 μg/kg/d; Group 3, leptin, 18.75 μg/kg/d; Group 4, leptin, 43.75 μg/kg/d. After a 14-day infusion, [¹⁴C] galactose and [¹⁴C] 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 ± SEM. Results: Systemic administration of increasing doses of leptin enhanced DNA content when compared with the appropriate control (group 2, 1.06 ± 0.04 [P < .05]; group 3, 1.1 ± 0.05 [P < .01]; and group 4, 1.07 ± 0.06 [P < .05]. Leptin enhanced mucosal absorptive function (galactose: group 2, 2.31 ± 0.15 [P < .01]; group 3, 2.71 ± 0.06 [P < .01]; group 4, 2.19 ± 0.28 [P < .05]; glycine: group 2, 2.34 ± 0,31 [P < .05]; group 3, 3.32 ± 0.14 [P < .01]; group 4, 3.1 ± 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.