[From Claude Bernard to the regulatory system between the hypothalamus and the periphery: implications for homeostasis of body weight and obesity].
The concept of interrelationships between the central nervous system and the periphery aimed at maintaining normal body weight homeostasis has been strengthened by the discovery of hypothalamic neuropeptide Y (NPY) and adipose tissue leptin. NPY, when infused intracerebroventricularly in normal animals produces hyperphagia and hormono-metabolic changes (hyperinsulinemia, hypercorticism) channeling nutrients preferentially toward lipogenesis and storage in adipose tissue and away from their utilization by muscles (muscle insulin resistance). Storage in NPY-infused rats is further favored by the observed decrease in the expression of uncoupling proteins. NPY-induced hyperinsulinemia and hypercorticosteronemia also promote leptin over-secretion. Released leptin, acting within the hypothalamus, decreases hypothalamic NPY levels (probably those of other hypothalamic neuropeptides as well), food intake, insulinemia, insulin sensitivity of white adipose tissue, while increasing that of muscles. Leptin acting centrally additionally favors the expression of uncoupling protein 1, 2, and 3, in keeping with an eflect on energy dissipating mechanisms. The respective hormono-metabolic eflects of NPY and leptin maintain a normal body homeostasis. In most obesity syndromes, the functional relationships between NPY and leptin are altered. Due to hypothalamic leptin receptor mutations or dysfunctions, leptin cannot exert its eflects: NPY levels (possibly those of other neuropeptides) remain elevated, maintaining excess storage, insulin as well as leptin resistance.
Jeanrenaud
B
B
Laboratoires de Recherches Métaboliques, Hôpital cantonal universitaire de Genève. bfjean@compuserve.com
Cusin
I
I
Rohner-Jeanrenaud
F
F
D000273:Adipose Tissue / Q000502:physiology*; D000818:Animals; D001835:Body Weight; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology; D005602:France; D049672:History, 19th Century; D049673:History, 20th Century; D006706:Homeostasis; D006801:Humans; D007031:Hypothalamus / Q000502:physiology* / Q000503:physiopathology; D020738:Leptin; D008954:Models, Biological; D009478:Neuropeptide Y / Q000502:physiology*; D009765:Obesity / Q000235:genetics / Q000503:physiopathology*; D010827:Physiology / Q000266:history; D011506:Proteins / Q000502:physiology*; D051381:Rats; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin
D002352:Carrier Proteins; D020738:Leptin; D009478:Neuropeptide Y; D011506:Proteins; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin
De Claude Bernard à la boucle régulatrice reliant l'hypothalamus à la périphérie: implications dans l'homéostasie du poids corporel et dans l'obésité.