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 intestin al proton-dependent transporter PepT1. We have examined the effects of lept in on PepT1 function in rat jejunum and in monolayers of the human enterocy te-like 2 cell Caco-2. Leptin is produced by the stomach and secreted in th e gut lumen. We show here that PepT1 and leptin receptors are expressed in Caco-2 and rat intestinal mucosal cells. Apical (but not basolateral) lepti n increased Caco-2 cell transport of cephalexin (CFX) and glycylsarcosine ( Gly-Sar), an effect that was associated with increased Gly-Sar uptake, incr eased membrane PepT1 protein, decreased intracellular PepT1 content, and no change in PepT1 mRNA levels. The maximal velocity (V-max) for Gly-Sar tran sport was significantly increased by leptin, whereas the apparent Michaelis -Menten constant (K-m) did not change. Furthermore, leptin-stimulated Gly S ar transport was completely suppressed by colchicine, which disrupts cellul ar 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 da ta revealed an unexpected action of gastric leptin in controlling ingestion of dietary proteins.