The hypothalamus and obesity.
Obesity, a condition already at epidemic proportions in the developed world, is largely attributable to an indulgent lifestyle. Biologically we feel hunger more acutely than feeling "full-up" (satiety). The discovery over a decade ago of leptin, an adiposity signal, revolutionised our understanding of hypothalamic mechanisms underpinning the central control of ingestive behaviour. The structure and function of many hypothalamic peptides (Neuropeptide Y (NPY), Melanocortins, Agouti related peptide (AGRP), Cocaine and amphetamine regulated transcript (CART), Melanin concentrating hormone (MCH), Orexins and endocannabinoids) have been characterised in rodent models. The pharmacological potential of several endogenous peripheral peptides released prior to, during and/or after feeding are being explored. Short-term signal hormones including Cholecystokinin (CCK), Ghrelin, Peptide YY (PYY(3-36)) and Glucagon-like peptide 1 (GLP-1) control meal size via pathways converging on the hypothalamus. Long-term regulation is provided by the main circulating hormones leptin and insulin. These systems among others, implicated in hypothalamic appetite regulation all provide potential "drugable" targets by which to treat obesity.
King
Peter J
PJ
Johnson & Johnson Pharmaceutical Research and Development, A Division of Janssen Pharmaceutica N.V., Metabolic Disorders, Turnhoutseweg 30, B-2340 Beerse, Belgium. pking3@prdbe.jnj.com
D000818:Animals; D001921:Brain / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology; D006801:Humans; D007031:Hypothalamus / Q000502:physiology*; D009765:Obesity / Q000503:physiopathology*; D017933:Peripheral Nervous System / Q000502:physiology