Role of islet-, gut-, and adipocyte-derived hormones in the central control of food intake and body weight: implications for an integrated neurohormonal approach to obesity pharmacotherapy.
Contrary to its historical epithet as a lifestyle disorder, obesity is now widely recognized as having a neurobiological basis. This progress is due to our knowledge not only about energy homoeostatic pathways within the central nervous system (CNS), but also about the role of peripheral peptide hormones acting upon the CNS. These hormones include long-term adiposity signals, such as leptin, that inform the CNS primarily of changes in the body's overall fat and energy reserves, and short-term signals such as amylin, peptide YY (PYY) and ghrelin, that primarily reflect changes in the immediate nutritive state (energy intake). The limited weight loss effects achieved with current monotherapy approaches to obesity have been attributed, at least in part, to the redundancies and potent counter-regulatory responses within the neurohormonal feedback loop governing energy balance. Recently, we reported that combinations of amylin, leptin and PYY(3-36) resulted in additive and/or synergistic interactions and caused marked weight loss in the diet-induced obese rat model, which to date has reasonably predicted the clinical effects of several hormones in obese humans. If confirmed in ongoing translational clinical research studies, these findings may provide a physiological rationale for a novel, integrated neurohormonal approach to pharmacotherapy for obesity.
Chen
Hubert C
HC
Amylin Pharmaceuticals, Inc. 9360 Towne Centre Drive, San Diego, CA 92121, USA.
Roth
Jonathan D
JD
Schroeder
Brock E
BE
Weyer
Christian
C
D017667:Adipocytes / Q000378:metabolism*; D054392:Adipokines / Q000502:physiology*; D001835:Body Weight / Q000502:physiology; D001921:Brain / Q000502:physiology; D002149:Energy Intake; D004734:Energy Metabolism; D005246:Feedback; D005768:Gastrointestinal Hormones / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007422:Intestines / Q000502:physiology*; D007515:Islets of Langerhans / Q000378:metabolism*; D020738:Leptin / Q000502:physiology; D008954:Models, Biological; D010187:Pancreatic Hormones / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
D054392:Adipokines; D005768:Gastrointestinal Hormones; D020738:Leptin; D010187:Pancreatic Hormones