Leptin Signaling in the Control of Metabolism and Appetite: Lessons from Animal Models

Obesity has become a major health concern in modern times, as it significantly increases the risk for the development of cardiovascular diseases, type 2 diabetes mellitus, and some types of cancer. The obesity epidemic has brought considerable attention to the molecular mechanisms through which adipocyte-secreted adipokines regulate physiological processes involved in metabolic and inflammatory diseases. Among them, leptin is considered as one of the principal regulators of a variety of physiological processes, including appetite and energy metabolism, through its binding to a variety of receptors and in particular by signaling through the long isoform receptor ObRb. Leptin signaling in the brain via ObRb plays an important role in the regulation of appetite and food intake, and involves several signaling pathways that either upregulate or attenuate leptin's anorexigenic response. This review describes ObRb-dependent, leptin-induced signaling pathways implicated in the control of appetite and energy metabolism in the organism, based on current information from animal models.