[Potential molecular targets for anti-obesity drugs--after the discovery of leptin].
The discovery of the adipose-derived hormone leptin has generated interest in the interaction between peripheral signals and brain targets involved in the regulation of feedings and energy balance. Potential anti-obesity drugs can be based on any intervention between the neuropeptide and its receptor that would alter the biological responses mediated by the neuronal network, in particular, food intake, metabolism and energy expenditure. Modulation of neurons in the arcuate nucleus by leptin results in reduced expression of neuropeptide Y and agouti-related protein, and increased expression of pro-opiomelanocortin (the precursor of a-melanocyte-stimulating hormone) and cocaine- and amphetamine- regulated transcript. Whether leptin finds its way into general usage as an anti-obesity drug, the use of modern methods to identify and target the components of leptin signaling pathway will form the basis for new pharmacological approaches to the treatment of obesity.
Hidaka
S
S
Department of Clinical Science and Medicine, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8507, Japan.
Ogawa
Y
Y
Nakao
K
K
D000818:Animals; D001067:Appetite Depressants / Q000493:pharmacokinetics*; D006801:Humans; D007028:Hypothalamic Hormones / Q000494:pharmacology; D020738:Leptin / Q000494:pharmacology; D008543:Melanins / Q000494:pharmacology; D009765:Obesity / Q000188:drug therapy; D010907:Pituitary Hormones / Q000494:pharmacology; D018043:Receptors, Corticotropin / Q000187:drug effects; D054411:Receptors, Leptin; D044101:Receptors, Melanocortin; D018013:Receptors, Neuropeptide / Q000187:drug effects
D001067:Appetite Depressants; D007028:Hypothalamic Hormones; C515448:LEPR protein, human; D020738:Leptin; D008543:Melanins; D010907:Pituitary Hormones; D018043:Receptors, Corticotropin; D054411:Receptors, Leptin; D044101:Receptors, Melanocortin; D018013:Receptors, Neuropeptide; C019463:melanin-concentrating hormone