Leptin inhibits glucose intestinal absorption via PKC, p38MAPK, PI3K and MEK/ERK

• Published in: PloS one Vol. 8; no. 12; p. e83360
• Main Authors: El-Zein, Ola, Kreydiyyeh, Sawsan Ibrahim
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 10-12-2013; Public Library of Science (PLoS)
• Subjects: 1-Phosphatidylinositol 3-kinase; Absorption; AKT protein; Biological Transport; Body weight; Caco-2 Cells; Diabetes; Extracellular signal-regulated kinase; Extracellular Signal-Regulated MAP Kinases - metabolism; Food intake; Glucose; Glucose - metabolism; Glucose - pharmacokinetics; Glucose transport; Humans; Inhibition; Insulin; Intestinal Absorption; Intestine; Kinases; Leptin; Leptin - physiology; Mucous Membrane - metabolism; Nutrients; p38 Mitogen-Activated Protein Kinases - metabolism; Penicillin; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation; Polyesters; Protein kinase C; Protein Kinase C - metabolism; Proteins; Rodents; Satiety; Signal Transduction; Signaling; Small intestine; Studies; Lebanon; Beirut Lebanon; California; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0083360

The role of leptin in controlling food intake and body weight is well recognized, but whether this is achieved by modulating nutrient absorption is still a controversial issue. The aim of this work was to investigate the direct effect of luminal leptin on glucose intestinal absorption and elucidate for the first time its signaling pathway. Fully differentiated Caco-2 cells grown on transwell filters were used for glucose transport studies. Leptin caused a significant reduction in glucose absorption. Individual and simultaneous inhibition of ERK, p38MAPK, PI3K or PKC abrogated completely the inhibitory effect of leptin. Activating PKC, lead to a stimulatory effect that appeared only when ERK, p38MAPK, or PI3K was inactive. Moreover, leptin increased the phosphorylation of ERK, Akt and p38MAPK. This increase changed into a decrease when p38MAPK and PKC were inactivated individually. Inhibiting ERK maintained the leptin-induced up-regulation of p-Akt and p-p38MAPK while inhibiting PI3K reduced the level of p-ERK and p-Akt but maintained the increase in p-p38MAPK. These results suggest that leptin reduces glucose absorption by activating PKC. Although the latter modulates glucose absorption via a stimulatory and an inhibitory pathway, only the latter is involved in leptin's action. Active PKC leads to a sequential activation of p38MAPK, PI3K and ERK which exerts an inhibitory effect on glucose absorption. The results reveal a modulatory role of leptin in nutrient absorption in addition to its known satiety inducing effect.