Insulin-stimulated leptin secretion requires calcium and PI3K-Akt activation

Numerous studies have focused on the regulation of leptin signaling and leptin functions in energy homeostasis. However, little is known about how leptin secretion is regulated. Here we studied leptin storage and secretion regulation in 3T3-L1 and primary adipocytes. Leptin is stored in membrane-bound vesicles that are localized predominantly in the endoplasmic reticulum (ER) and close to the plasma membrane of both 3T3-L1 and primary adipocytes. Insulin increases leptin secretion as early as 15 min without affecting the leptin mRNA level. Interestingly, protein synthesis inhibitor cycloheximide and ER-Golgi trafficking blocker Brefeldin-A treatment inhibit both basal and insulin-stimulated leptin secretion (ISLS), suggesting that insulin stimulates leptin secretion by up-regulating leptin synthesis and that leptin-containing vesicles go through ER-Golgi route. The phosphoinositide 3-kinase (PI3K)-Akt but not MAPK pathway is involved in ISLS in vitro and in vivo. Although Ca2+ triggers synaptic vesicle and secretory granule exocytosis, Ca2+ influx alone is not sufficient to induce leptin secretion. Remarkably, Ca2+ is required for ISLS possibly due to its involvement in insulin-stimulated Akt phosphorylation.We conclude that insulin stimulates leptin release through the PI3K-Akt pathway and that Ca2+ is required for robust Akt phosphorylation and leptin secretion.
Source: BJ Cell - Category: Biochemistry Authors: Tags: BJ Cell Source Type: research