PepT1-mediated epithelial transport of dipeptides and cephalexin is enhanced by luminal leptin in the small intestine.
Dietary proteins are mostly absorbed as di- and tripeptides by the intestinal proton-dependent transporter PepT1. We have examined the effects of leptin on PepT1 function in rat jejunum and in monolayers of the human enterocyte-like 2 cell Caco-2. Leptin is produced by the stomach and secreted in the gut lumen. We show here that PepT1 and leptin receptors are expressed in Caco-2 and rat intestinal mucosal cells. Apical (but not basolateral) leptin increased Caco-2 cell transport of cephalexin (CFX) and glycylsarcosine (Gly-Sar), an effect that was associated with increased Gly-Sar uptake, increased membrane PepT1 protein, decreased intracellular PepT1 content, and no change in PepT1 mRNA levels. The maximal velocity (Vmax) for Gly-Sar transport was significantly increased by leptin, whereas the apparent Michaelis-Menten constant (Km) did not change. Furthermore, leptin-stimulated Gly-Sar transport was completely suppressed by colchicine, which disrupts cellular translocation of proteins to plasma membranes. Intrajejunal leptin also induced a rapid twofold increase in plasma CFX after jejunal perfusion with CFX in the rat, indicating enhanced intestinal absorption of CFX. These data revealed an unexpected action of gastric leptin in controlling ingestion of dietary proteins.
Buyse
M
M
Institut National de la Santé et de la Recherche Médicale Unité 410, Faculté de Médecine Xavier Bichat, Paris, France.
Berlioz
F
F
Guilmeau
S
S
Tsocas
A
A
Voisin
T
T
Péranzi
G
G
Merlin
D
D
Laburthe
M
M
Lewin
M J
MJ
Rozé
C
C
Bado
A
A
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001692:Biological Transport; D020126:Brefeldin A / Q000494:pharmacology; D018938:Caco-2 Cells; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D002506:Cephalexin / Q000378:metabolism*; D003078:Colchicine / Q000494:pharmacology; D017931:DNA Primers; D004151:Dipeptides / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007421:Intestine, Small / Q000378:metabolism / Q000502:physiology*; D020738:Leptin / Q000502:physiology*; D008969:Molecular Sequence Data; D000074011:Peptide Transporter 1; D051381:Rats; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D027981:Symporters
D002352:Carrier Proteins; D017931:DNA Primers; D004151:Dipeptides; C515448:LEPR protein, human; D020738:Leptin; D000074011:Peptide Transporter 1; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; C082186:SLC15A1 protein, human; C489940:Slc15a1 protein, rat; D027981:Symporters; D020126:Brefeldin A; D002506:Cephalexin; D003078:Colchicine