Anabolic neuropeptides.
The hypothalamus and other brain regions that control energy homeostasis contain neuronal populations that produce specific neuropeptides which have experimental effects on feeding behavior and body weight. Here, we describe examples of neuropeptides that exert 'anabolic' effects, notably stimulation of feeding and increased body weight. Neuropeptide Y (NPY) neurons in the hypothalamic arcuate nucleus (ARC) are inhibited by leptin and insulin, and thus are stimulated in states of energy deficit and fat loss, e.g., underfeeding. NPY neuronal overactivity contributes to enhanced hunger and food-seeking activity under these conditions. The lateral hypothalamic area (LHA) contains specific neuronal populations that affect feeding in different ways. Neurons expressing the appetite-stimulating peptide orexin A are stimulated by starvation (but not food restriction) and by hypoglycemia, but only if food is withheld. Orexin neurons are apparently activated by low glucose but are promptly inhibited by visceral feeding signals, probably mediated via vagal sensory pathway and the nucleus of the solitary tract (NTS); a short-term role in initiating feeding seems most likely. Other LHA neurons express melanin-concentrating hormone (MCH), which transiently increases food intake when injected centrally. MCH neurons may be regulated by leptin, insulin and glucose. Glucose-sensing neurons in the hypothalamus and elsewhere are sensitive to other cues of nutritional state, including visceral satiety signals (transmitted via the vagus) and orexin A. Thus, long- and short-term humoral and neural signals interact with each other to meet diverse nutritional needs, and anabolic neuropeptides are important in the overall integration of energy homeostasis. Clarifying the underlying mechanisms will be essential to understanding normal energy balance and the pathogenesis and treatment of disorders, such as obesity and cachexia.
Williams
Gareth
G
Diabetes and Endocrinology Research Group, Department of Medicine, University of Liverpool, Duncan Building, Daulby Street, Liverpool L69 3GA, UK. harrold@liverpool.ac.uk
Cai
Xue J
XJ
Elliott
Joanne C
JC
Harrold
Joanne A
JA
D045930:Anabolic Agents / Q000378:metabolism*; D000818:Animals; D001835:Body Weight / Q000502:physiology*; D002352:Carrier Proteins / Q000502:physiology; D005247:Feeding Behavior / Q000502:physiology*; D007028:Hypothalamic Hormones / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D008543:Melanins / Q000502:physiology; D009478:Neuropeptide Y / Q000502:physiology; D009479:Neuropeptides / Q000502:physiology*; D000068797:Orexins; D010907:Pituitary Hormones / Q000502:physiology
D045930:Anabolic Agents; D002352:Carrier Proteins; D007028:Hypothalamic Hormones; D047908:Intracellular Signaling Peptides and Proteins; D008543:Melanins; D009478:Neuropeptide Y; D009479:Neuropeptides; D000068797:Orexins; D010907:Pituitary Hormones; C019463:melanin-concentrating hormone