Luminal leptin inhibits intestinal sugar absorption in vivo.
OBJECTIVE
We have previously demonstrated that leptin inhibits galactose absorption in rat intestinal everted rings and that leptin receptors are present in the apical membrane of the enterocytes. This adipocyte-derived hormone is also secreted by gastric mucosal cells and is able to reach the intestinal lumen. The goal of the present study was to prove whether luminal leptin acts on intestinal sugar absorption in vivo both at low (basal state) and high sugar concentration (post-prandial state).


METHODS
In vivo intestinal sugar absorption in rat was measured with recirculating and single-pass perfusion systems. Sugar disappearance in the perfusate was measured by radioactivity and biochemical methods. Luminal leptin effect on intestinal absorption mediated by sodium-dependent glucose transporter 1 (SGLT1) and glucose transporter 2 (GLUT2) as well as intestinal permeability (mannitol absorption) was determined.


RESULTS
Luminal leptin inhibited intestinal sugar absorption at low galactose concentrations, which indicates that leptin regulates SGLT1 activity in vivo. The inhibition was reversed in the absence of hormone in the intestinal lumen, suggesting that it was produced by post-translational regulation processes. At high luminal glucose concentrations, leptin also inhibited the phloretin-insensitive component of sugar absorption mediated by SGLT1. There was no significant effect on the apical GLUT2 component of absorption. Leptin did not modify in vivo intestinal permeability determined with (14)C-mannitol.


CONCLUSIONS
These observations support the view that gastric leptin exerts a regulatory role on intestinal sugar absorption in the postprandial state by modifying the active component of absorption.
Iñigo
C
C
Department of Physiology and Nutrition, University of Navarra, Pamplona, Spain.
Patel
N
N
Kellett
G L
GL
Barber
A
A
Lostao
M P
MP
D000818:Animals; D002463:Cell Membrane Permeability; D004305:Dose-Response Relationship, Drug; D020895:Enterocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D005690:Galactose / Q000493:pharmacokinetics*; D051273:Glucose Transporter Type 2 / Q000235:genetics / Q000378:metabolism; D007408:Intestinal Absorption / Q000502:physiology*; D007422:Intestines / Q000166:cytology / Q000502:physiology; D020738:Leptin / Q000502:physiology*; D008297:Male; D008353:Mannitol / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D051269:Sodium-Glucose Transporter 1 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
D051273:Glucose Transporter Type 2; D020738:Leptin; C495683:Slc2a2 protein, rat; C495676:Slc5a1 protein, rat; D051269:Sodium-Glucose Transporter 1; D008353:Mannitol; D005690:Galactose