Leptin: a new growth factor for the small intestine.
OBJECTIVE
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.
Alavi
Karim
K
Department of Surgery and Musculoskeletal Inherited Disease Laboratories at the Alfred I. DuPont Hospital for Children, Wilmington, DE, USA.
Schwartz
Marshall Z
MZ
Prasad
Rajeev
R
O'connor
Darlise
D
Funanage
Vicky
V
D000818:Animals; D004247:DNA / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D020869:Gene Expression Profiling; D005947:Glucose / Q000378:metabolism; D051296:Glucose Transporter Type 5; D006133:Growth Substances / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000502:physiology*; D007262:Infusions, Intravenous; D007413:Intestinal Mucosa / Q000737:chemistry / Q000378:metabolism; D007421:Intestine, Small / Q000737:chemistry / Q000254:growth & development* / Q000378:metabolism; D020738:Leptin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000502:physiology*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D009004:Monosaccharide Transport Proteins / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D051269:Sodium-Glucose Transporter 1
D051296:Glucose Transporter Type 5; D006133:Growth Substances; D020738:Leptin; D008562:Membrane Glycoproteins; D009004:Monosaccharide Transport Proteins; C495676:Slc5a1 protein, rat; D051269:Sodium-Glucose Transporter 1; D004247:DNA; D005947:Glucose