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.

Chronic Intake of Commercial Sweeteners Induces Changes in Feeding Behavior and Signaling Pathways Related to the Control of Appetite in BALB/c Mice.

Nonnutritive sweetener use is a common practice worldwide. Although considered safe for human consumption, accumulating evidence suggests these compounds may affect metabolic homeostasis; however, there is no consensus on the role of frequent sweetener intake in appetite and weight loss. We sought to determine whether frequent intake of commercial sweeteners induces changes in the JAK2/STAT3 signaling pathway in the brain of mice, as it is involved in the regulation of appetite and body composition. We supplemented adult BALB/c mice with sucrose, steviol glycosides (SG), or sucralose, daily, for 6 weeks. After supplementation, we evaluated body composition and expression of total and phosphorylated JAK2, STAT3, and Akt, as well as SOCS3 and ObRb, in brain tissue. Our results show that frequent intake of commercial SG decreases energy intake, adiposity, and weight gain in male animals, while increasing the expression of pJAK2 and pSTAT3 in the brain, whereas sucralose increases weight gain and pJAK2 expression in females. Our results suggest that chronic intake of commercial sweeteners elicits changes in signaling pathways that have been related to the control of appetite and energy balance in vivo, which may have relevant consequences for the nutritional state and long term health of the organism.