Kansas State University
Protein Interactions that Regulate Leptin Secretion (2004-06)
Leptin is a small protein of 16 kDa produced by adipocytes that has profound physiological effects in regulating food intake, weight balance and energy expenditure, reproduction and immune responses. Leptin deficient (ob/ob) mice display hyperphagia, marked obesity and insulin resistance which are reversed upon recombinant leptin administration. In addition, leptin participates in the regulation of whole body insulin sensitivity with profound implications in type 2 diabetes. Recent data also suggests that excess of leptin may be involved in inflammatory responses associated with type 1 diabetes. The physiological functions of leptin are well documented, however little is known about the molecular mechanisms of traffic and secretion. Dr. Mora's group has analyzed the intracellular compartmentalization of leptin in 3T3L1 adipocytes. Their preliminary data indicates that leptin accumulates in the endoplasmic reticulum in the steady state but is secreted following the classical secretory pathway that involves the synthesis in the rough endoplasmic reticulum and transport to the Golgi apparatus and Trans Golgi Network (TGN). Dr. Mora's group will use a proteomic approach to: 1) identify proteins that bind to leptin and that play a role in the synthesis, folding traffic and secretion of leptin; and 2) determine the regions/domains that are important for leptin compartmentalization and traffic in adipocytes.
Understanding the molecular basis of how leptin synthesis and secretion is regulated will allow the development of therapeutic interventions that will target these molecules to modulate leptin circulating levels in people affected by obesity and obesity-related disorders such as diabetes.