Acute and chronic administration of melanin-concentrating hormone enhances food intake and body weight in Wistar and Sprague–Dawley rats

AIM: Although melanin-concentrating hormone (MCH) is believed to be an important regulator of feeding behavior, both its acute and chronic effects on food intake as well as its interaction with other brain peptides involved in the control of appetite remain unclear. Therefore, the acute effects of MCH on food intake and the chronic effect of MCH on food intake and the gene expression of various hypothalamic peptides involved in the control of appetite were studied in rats.METHODS AND RESULTS: Either the acute or the continuous intraventricular infusion of MCH for 12 days stimulated feeding in both Wistar or Sprague–Dawley rats. Removal of the hypothalamus at the end of the chronic infusion studies allowed measurement of the expression of mRNAs encoding for MCH, neuropeptide Y (NPY), orexin, agouti gene-related peptide, cocaine and amphetamine-related transcript and neurotensin–neuropeptides involved in the control of appetite. Chronic intraventricular infusion of MCH activated only NPY mRNA synthesis in Sprague–Dawley rats. The increase in food intake in response to MCH in Sprague–Dawley rats did not appear to be due to the release of NPY since combination studies demonstrated consistently additive effects of the two peptides on food intake at maximum or near maximum doses.CONCLUSIONS: These results strongly suggest that MCH is an orexigenic peptide involved in the control of both short- and long term food intake in satiated rats and further indicate that the MCH pathway is a possible target for the control of food intake and obesity.

[1]  E. Kühn,et al.  Endocrine differences between the Wistar and Sprague-Dawley laboratory rat: influence of cold adaptation. , 1983, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[2]  N. Tritos,et al.  Two important systems in energy homeostasis: melanocortins and melanin-concentrating hormone , 1999, Neuropeptides.

[3]  B. Lowell,et al.  Mice lacking melanin-concentrating hormone are hypophagic and lean , 1998, Nature.

[4]  C. Broberger Hypothalamic cocaine- and amphetamine-regulated transcript (CART) neurons: histochemical relationship to thyrotropin-releasing hormone, melanin-concentrating hormone, orexin/hypocretin and neuropeptide Y , 1999, Brain Research.

[5]  D. Vicent,et al.  Functional interactions between melanin-concentrating hormone, neuropeptide Y, and anorectic neuropeptides in the rat hypothalamus. , 1998, Diabetes.

[6]  J. Fauchère,et al.  Appetite suppression based on selective inhibition of NPY receptors , 2002, International Journal of Obesity.

[7]  T. Hökfelt,et al.  Effect of 2‐mercaptoacetate and 2‐deoxy‐D‐glucose administration on the expression of NPY, AGRP, POMC, MCH and hypocretin/orexin in the rat hypothalamus , 2000, Neuroreport.

[8]  A. Yamanaka,et al.  Mice lacking the M3 muscarinic acetylcholine receptor are hypophagic and lean , 2001, Nature.

[9]  J. Vaughan,et al.  The melanin‐concentrating hormone system of the rat brain: An immuno‐ and hybridization histochemical characterization , 1992, The Journal of comparative neurology.

[10]  S. Nicolaidis,et al.  Melanin-concentrating hormone is a potent anorectic peptide regulated by food-deprivation and glucopenia in the rat , 1996, Neuroscience.

[11]  F. Leslie,et al.  Expression of the melanin‐concentrating hormone (MCH) receptor mRNA in the rat brain , 2001, The Journal of comparative neurology.

[12]  S. Bloom,et al.  Investigation of the feeding effects of melanin concentrating hormone on food intake — action independent of galanin and the melanocortin receptors , 1999, Brain Research.

[13]  G. Barsh,et al.  Chemically defined projections linking the mediobasal hypothalamus and the lateral hypothalamic area , 1998, The Journal of comparative neurology.

[14]  A. Sahu Leptin decreases food intake induced by melanin-concentrating hormone (MCH), galanin (GAL) and neuropeptide Y (NPY) in the rat. , 1998, Endocrinology.

[15]  L. de Lecea,et al.  Mapping of the mRNAs for the hypocretin/orexin and melanin‐concentrating hormone receptors: Networks of overlapping peptide systems , 2001, The Journal of comparative neurology.

[16]  S. Gammeltoft,et al.  A role for melanin-concentrating hormone in the central regulation of feeding behaviour , 1996, Nature.

[17]  N. Levens,et al.  The regulatory role of leptin in food intake. , 1998, Current opinion in clinical nutrition and metabolic care.

[18]  T. Miyoshi,et al.  Printed in U.S.A. Copyright © 1997 by The Endocrine Society Melanin-Concentrating Hormone Acutely Stimulates Feeding, But Chronic Administration Has No Effect on , 2022 .

[19]  J. Vaughan,et al.  Characterization of melanin-concentrating hormone from rat hypothalamus. , 1989, Endocrinology.

[20]  B. Lowell,et al.  Melanin-concentrating hormone overexpression in transgenic mice leads to obesity and insulin resistance. , 2001, The Journal of clinical investigation.

[21]  L. Iversen,et al.  REGIONAL STUDIES OF CATECHOLAMINES IN THE RAT BRAIN‐I , 1966, Journal of neurochemistry.

[22]  C. Saper,et al.  From Lesions to Leptin Hypothalamic Control of Food Intake and Body Weight , 1999, Neuron.

[23]  P. Sawchenko,et al.  Rat melanin-concentrating hormone messenger ribonucleic acid expression: marked changes during development and after stress and glucocorticoid stimuli. , 1992, Endocrinology.