The Role of Snare Complex in Leptin Secretion

The adipose tissue is now recognized as an endocrine organ due to its active secretion of many important peptide hormones, collectively named adipokines, which regulate many physiological functions. Despite an increasing number of adipokines has been discovered in the past decades, the secretory mechanism of adipocytes remains poorly understood. Leptin is primarily secreted by adipocytes to regulate energy balance. Its secretion is closely regulated by many physiological modulators, including hormones, nutrients, and neuronal stimuli. However the molecular mechanism regulating leptin secretion in adipocytes remains poorly understood. N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) are known to mediate exocytosis in many neuronal and endocrine systems. They also play a role in cytokine secretion in immune cells. In adipocytes, the SNARE complex also mediates insulin-stimulated translocation of glucose transporter 4 (GLUT4). However, the role of the SNARE complex in secretion of adipokines has not been studied. Using differentiated 3T3-L1 adipocytes as the model system to study the secretory mechanism of leptin, we found that the SNARE complex might be involved in basal and insulin-stimulated secretion of leptin in adipocytes. To further elucidate the molecular mechanism Therefore this grant proposal aims to address the following three questions: (1) to characterize the SNARE complex involved in leptin trafficking and secretion, (2) to elucidate how the SNARE complex is regulated by physiological modulators to facilitate leptin secretion, and (3) finally to understand how the SNARE complex regulates leptin secretion in primary adipocytes, and its regulation in diet-induced obese mice and mice at feeding/fasting cycles. This study will not only provide insight on the molecular mechanism controlling leptin secretion under normal and pathological conditions, but also provide new therapeutic methods in treating the diseases in the future.

Project ID:PC10108-0824
External Project ID:NSC101-2320-B182-007