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 periphery, notably via the hormone leptin, which is synthesized in and secreted from adipose tissue. Under normal conditions, a dynamic equilibrium exists between anabolic neuropeptides (orexigenic peptides), which favor food intake, decrease energy expenditure, and facilitate fat storage, and catabolic ones (anorexigenic peptides), which decrease food intake, increase energy expenditure, 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 isoform. After a specific signaling cascade, leptin inhibits many of the orexigenic neuropeptides while favoring many of the anorexigenic ones. Thus, leptin decreases food intake and body weight, and it increases fat oxidation and energy expenditure, ultimately favoring leanness. Lack of leptin secretion, the inability of leptin to reach the brain, or the inability of leptin to interact with hypothalamic leptin receptors, prevent leptin's effects and lead to obesity.
Jeanrenaud
B
B
Geneva University, Chemin des Piverts 6, 1226 Geneva, Switzerland. jeanrenaud.bf@vtx.ch
Rohner-Jeanrenaud
F
F
D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000502:physiology; D004435:Eating / Q000502:physiology*; D004734:Energy Metabolism / Q000502:physiology*; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007028:Hypothalamic Hormones / Q000502:physiology; D020738:Leptin / Q000502:physiology* / Q000627:therapeutic use; D008543:Melanins / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000502:physiology; D009478:Neuropeptide Y / Q000502:physiology; D009479:Neuropeptides / Q000502:physiology*; D009765:Obesity / Q000378:metabolism* / Q000517:prevention & control*; D018847:Opioid Peptides / Q000502:physiology; D010907:Pituitary Hormones / Q000502:physiology; D000521:alpha-MSH / Q000502:physiology; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
D007028:Hypothalamic Hormones; D020738:Leptin; D008543:Melanins; D009419:Nerve Tissue Proteins; D009478:Neuropeptide Y; D009479:Neuropeptides; D018847:Opioid Peptides; D010907:Pituitary Hormones; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D000521:alpha-MSH; C019463:melanin-concentrating hormone; D003346:Corticotropin-Releasing Hormone