Central and peripheral dysregulation of melanin-concentrating hormone in obese Zucker rats.
Melanin concentrating hormone (MCH) is a peptide synthesized in the lateral hypothalamus which stimulates food ingestion and leptin secretion in rodents. In this experiment, we measured the expressions of MCH as well as of its receptor (SLC-1) in the hypothalamus of obese hyperphagic and lean Zucker rats by quantitative real time RT-PCR. MCH mRNA expression in the obese rats was significantly increased by a factor of five (P<0.01) whereas expression of SLC-1 was decreased by more than 50% (P<0.05). Circulating levels of leptin and MCH were increased in the plasma of obese Zucker rats when compared to lean rats (38-fold and 1.7-fold, respectively, P<0.001 and P<0.01). However, individual MCH levels were not directly correlated to leptin levels in the lean (functional leptin receptor) or in the obese (non-functional leptin receptor) Zucker rats. These results indicate that the absence of leptin signaling in rats is associated with an increased hypothalamic expression and circulating release of MCH, contributing to their obesity syndrome.
Stricker-Krongrad
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Metabolic Diseases Physiology and Pharmacology, Millennium Pharmaceuticals, 75 Sidney Street, Cambridge, MA 02139, USA. krongrad@mpi.com
Dimitrov
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Beck
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D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D005838:Genotype; D007026:Hypothalamic Area, Lateral / Q000378:metabolism*; D007028:Hypothalamic Hormones / Q000378:metabolism*; D020738:Leptin / Q000097:blood / Q000378:metabolism; D008297:Male; D008543:Melanins / Q000378:metabolism*; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D010907:Pituitary Hormones / Q000378:metabolism*; D017354:Point Mutation; D011498:Protein Precursors / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D011979:Receptors, Pituitary Hormone / Q000378:metabolism
D002352:Carrier Proteins; D007028:Hypothalamic Hormones; D020738:Leptin; D008543:Melanins; D010907:Pituitary Hormones; D011498:Protein Precursors; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D011979:Receptors, Pituitary Hormone; C092274:melanin-concentrating hormone receptor; C019463:melanin-concentrating hormone