Effects of neuropeptides and leptin on nutrient partitioning: Dysregulations in obesity

Body weight homeostasis is maintained via a series of complex interactions that occur between the brain (particularly the hypothalamus) and the periph ery, notably via the hormone leptin, which is synthesized in and secreted f rom adipose tissue. Under normal conditions, a dynamic equilibrium exists b etween anabolic neuropeptides (orexigenic peptides), which favor food intak e, decrease energy expenditure, and facilitate fat storage, and catabolic o nes (anorexigenic peptides), which decrease food intake, increase energy ex penditure, and facilitate the loss of fat stores. Secreted leptin, although it may have some direct peripheral effects, exerts its action principally within the brain. Following its transport through the blood-brain barrier, leptin reaches the hypothalamic area, where it binds to its long receptor i soform. After a specific signaling cascade, leptin inhibits many of the ore xigenic neuropeptides while favoring many of the anorexigenic ones. Thus, l eptin decreases food intake and body weight, and it increases fat oxidation and energy expenditure, ultimately favoring leanness. Lack of leptin secre tion, the inability of leptin to reach the brain, or the inability of lepti n to interact with hypothalamic leptin receptors, prevent leptin's effects and lead to obesity.