Skip to main content

Melanin-concentrating hormone neuron system: the wide web that controls the feeding

Anatomical Science International volume 77, pages 149–160 (2002)Cite this article

Abstract

Recent evidence indicates that the hypothalamic control system of food intake involves many feeding-related neuropeptides. Melanin-concentrating hormone (MCH), one of a group of potent orexigenic peptides, is exclusively produced in neurons of the lateral hypothalamic area that give off fibers to the widespread brain regions. The receptor of MCH was recently identified to be localized in cell bodies and dendritic processes of particular neurons throughout the brain, in close spatial relation to MCH fibers. Leptin, an anorectic hormone secreted from the adipose tissue, acts on the specific receptor present on its target neurons in the brain, and suppresses the expression of both MCH and its receptor. Leptin receptor and STAT3, a transcription factor mediating the leptin signaling, are distributed in the widespread brain regions including the cerebral neocortex, hippocampal formation and lower brainstem as well as the hypothalamus where MCH fibers and the MCH receptor are abundantly present. These findings suggest that MCH exerts the effect through its specific receptor distributed throughout the brain and that the function of MCH is influenced by the condition of peripheral energy balance via leptin, the leptin receptor and STAT3, not only in the hypothalamus, but also in other brain regions. In the brain, MCH might be involved in various feeding-related functions, such as appetite, food-searching behavior, eating muscle movement, and control of energy balance, depending upon the physiological role of each region.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

References

  • Ahima RS, Prabakaran D, Mantzoros C et al. (1996) Role of leptin in the neuroendocrine response to fasting. Nature 18, 250–2.

    Article  Google Scholar 

  • An S, Cutler G, Zhao JJ et al. (2001) Identification and characterization of a melanin-concentrating hormone receptor. Proc Natl Acad Sci USA 98, 7576–81.

    PubMed  Article  CAS  Google Scholar 

  • Anand BK, Brobeck JR (1951) Hypothalamic control of food intake in rats and cats. Yale J Biol Med 24, 123–40.

    PubMed  CAS  Google Scholar 

  • Bachner D, Kreienkamp H, Weise C, Buck F, Richter D (1999) Identification of melanin concentrating hormone (MCH) as the natural ligand for the orphan somatostatin-like receptor 1 (SLC-1). FEBS Lett 3, 522–4.

    Article  Google Scholar 

  • Bai FL, Yamano M, Shiotani Y et al. (1985) An arcuato-paraventricular and dorsomedial hypothalamic neuropeptide Y-containing system which lacks noradrenaline in the rat. Brain Res 331, 172–5.

    PubMed  Article  CAS  Google Scholar 

  • Baker BI (1993) The role of melanin-concentrating hormone in color change. Ann NY Acad Sci 680, 279–89.

    PubMed  Article  CAS  Google Scholar 

  • Banks AS, Davis SM, Bates SH, Myers MG Jr (2000) Activation of downstream signals by the long form of the leptin receptor. J Biol Chem 275, 14 563–72.

    Google Scholar 

  • Banks WA, Kastin AJ, Huang W, Jaspan JB, Maness LM (1996) Leptin enters the brain by a saturable system independent of insulin. Peptides 17, 305–11.

    PubMed  Article  CAS  Google Scholar 

  • Beltt BM, Keesey RE (1975) Hypothalamic map of stimulation current thresholds for inhibition of feeding in rats. Am J Physiol 229, 1124–33.

    PubMed  CAS  Google Scholar 

  • Bittencourt JC, Presse F, Arias C et al. (1992) The melanin-concentrating hormone system of the rat brain: an immunoand hybridization histochemical characterization. J Comp Neurol 319, 218–45.

    PubMed  Article  CAS  Google Scholar 

  • Broberger C, De Lecea L, Sutcliffe JG, Hokfelt T (1998) Hypocretin/orexin- and melanin-concentrating hormone-expressing cells form distinct populations in the rodent lateral hypothalamus: relationship to the neuropeptide Y and agouti gene-related protein systems. J Comp Neurol 402, 460–74.

    PubMed  Article  CAS  Google Scholar 

  • Buyse M, Ovesjo ML, Goiot H et al. (2001) Expression and regulation of leptin receptor proteins in afferent and efferent neurons of the vagus nerve. Eur J Neurosci 14, 64–72.

    PubMed  Article  CAS  Google Scholar 

  • Campfield LA, Smith FJ, Guisez Y, Devos R, Burn P (1995) Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks. Science 269, 546–9.

    PubMed  Article  CAS  Google Scholar 

  • Chambers J, Ames RS, Bergsma D et al. (1999) Melanin-concentrating hormone is the cognate ligand for the orphan G-protein-coupled receptor SLC-1. Nature 400, 261–5.

    PubMed  Article  CAS  Google Scholar 

  • Chemelli RM, Willie JT, Sinton CM et al. (1999) Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. Cell 98, 437–51.

    PubMed  Article  CAS  Google Scholar 

  • Elias CF, Aschkenasi C, Lee C et al. (1999) Leptin differentially regulates NPY and POMC neurons projecting to the lateral hypothalamic area. Neuron 23, 775–86.

    PubMed  Article  CAS  Google Scholar 

  • Elias CF, Saper CB, Maratos-Flier E et al. (1998) Chemically defined projections linking the mediobasal hypothalamus and the lateral hypothalamic area. J Comp Neurol 402, 442–59.

    PubMed  Article  CAS  Google Scholar 

  • Elmquist JK, Elias CF, Saper CB (1999) From lesions to leptin: hypothalamic control of food intake and body weight. Neuron 22, 221–32.

    PubMed  Article  CAS  Google Scholar 

  • Fekete C, Legradi G, Mihaly E et al. (2000a) Alpha-Melanocyte-stimulating hormone is contained in nerve terminals innervating thyrotropin-releasing hormone-synthesizing neurons in the hypothalamic paraventricular nucleus and prevents fasting-induced suppression of prothyrotropin-releasing hormone gene expression. J Neurosci 20, 1550–8.

    PubMed  CAS  Google Scholar 

  • Fekete C, Legradi G, Mihaly E, Tatro JB, Rand WM, Lechan RM (2000b) Alpha-melanocyte stimulating hormone prevents fasting-induced suppression of corticotropin-releasing horm one gene expression in the rat hypothalamic paraventricular nucleus. Neurosci Lett 289, 152–6.

    PubMed  Article  CAS  Google Scholar 

  • Flier JS, Maratos-Flier E (1998) Obesity and the hypothalamus: novel peptides for new pathways. Cell 92, 437–40.

    PubMed  Article  CAS  Google Scholar 

  • Gold (1973) Hypothalamic obesity: The myth of the ventromedial nucleus. Science 182, 488–90.

    PubMed  Article  CAS  Google Scholar 

  • Grill HJ, Schwartz MW, Kaplan JM, Foxhall JS, Breininger J, Baskin DG (2002) Evidence that the caudal brainstem is a target for the inhibitory effect of leptin on food intake. Endocrinology 143, 239–46.

    PubMed  Article  CAS  Google Scholar 

  • Guan XM, Hess JF, Yu H, Hey PJ, van der Ploeg LH (1997) Differential expression of mRNA for leptin receptor isoforms in the rat brain. Mol Cell Endocrinol 133, 1–7.

    PubMed  Article  CAS  Google Scholar 

  • Hakansson ML, Brown H, Ghilardi N, Skoda RC, Meister B (1998) Leptin receptor immunoreactivity in chemically defined target neurons of the hypothalamus. J Neurosci 18, 559–72.

    PubMed  CAS  Google Scholar 

  • Hakansson ML, de Lecea L, Sutcliffe JG, Yanagisawa M, Meister B (1999) Leptin receptor- and STAT3-immunoreactivities in hypocretin/orexin neurones of the lateral hypothalamus. J Neuroendocrinol 11, 653–63.

    PubMed  Article  CAS  Google Scholar 

  • Hakansson ML, Meister B (1998) Transcription factor STAT3 in leptin target neurons of the rat hypothalamus. Neuroendocrinology 68, 420–7.

    PubMed  Article  CAS  Google Scholar 

  • Hakansson-Ovesjo ML, Collin M, Meister B (2000) Down-regulated STAT3 messenger ribonucleic acid and STAT3 protein in the hypothalamic arcuate nucleus of the obese leptin-deficient (ob/ob) mouse. Endocrinology 141, 3946–55.

    PubMed  Article  CAS  Google Scholar 

  • Halaas JL, Gajiwala KS, Maffei M et al. (1995) Weight-reducing effects of the plasma protein encoded by the obese gene. Science 269, 543–6.

    PubMed  Article  CAS  Google Scholar 

  • Hanada R, Nakazato M, Matsukura S, Murakami N, Yoshimatsu H, Sakata T (2000) Differential regulation of melanin-concentrating hormone and orexin genes in the agouti-related protein/melanocortin-4 receptor system. Biochem Biophys Res Comm 268, 88–91.

    PubMed  Article  CAS  Google Scholar 

  • Hara J, Beuckmann CT, Nambu T et al. (2001) Genetic ablation of orexin neurons in mice results in narcolepsy, hypophagia, and obesity. Neuron 30, 345–54.

    PubMed  Article  CAS  Google Scholar 

  • Hervieu GJ, Cluderay JE, Harrison D et al. (2000) The distribution of the mRNA and protein products of the melanin-concentrating hormone (MCH) receptor gene, slc-1, in the central nervous system of the rat. Eur J Neurosci 12, 1194–216.

    PubMed  Article  CAS  Google Scholar 

  • Hetherington AW, Ranson SW (1940) Hypothalamic lesions and adiposity in the rat. Anat Rec 78, 149–72.

    Article  Google Scholar 

  • Hill J, Duckworth M, Murdock P et al. (2001) Molecular cloning and functional characterization of MCH2, a novel human MCH receptor. J Biol Chem 276, 20125–9.

    PubMed  Article  CAS  Google Scholar 

  • Hubschle T, Thom E, Watson A, Roth J, Klaus S, Meyerhof W (2001) Leptin-induced nuclear translocation of STAT3 immunoreactivity in hypothalamic nuclei involved in body weight regulation. J Neurosci 21, 2413–24.

    PubMed  CAS  Google Scholar 

  • Inui A (1999) Feeding and body-weight regulation by hypothalamic neuropeptides — mediation of the actions of leptin. Trends Neurosci 22, 62–7.

    PubMed  Article  CAS  Google Scholar 

  • Kalra SP, Dube MG, Pu S, Xu B, Horvath TL, Kalra PS (1999) Interacting appetite-regulating pathways in the hypothalamic regulation of body weight. Endocrinol Rev 20, 68–100.

    Article  CAS  Google Scholar 

  • Kawauchi H, Kawazoe I, Tsubokawa M, Kishida M, Baker BI (1983) Characterization of melanin-concentrating hormone in chum salmon pituitaries. Nature 305, 321–3.

    PubMed  Article  CAS  Google Scholar 

  • Kim EM, Welch CC, Grace MK, Billington CJ, Levine AS (1996) Chronic food restriction and acute food deprivation decrease mRNA levels of opioid peptides in arcuate nucleus. Am J Physiol 270, R1019–24.

    PubMed  CAS  Google Scholar 

  • Kiss JZ, Cassell MD, Palkovits M (1984) Analysis of the ACTH/beta-End/alpha-MSH -immunoreactive afferent input to the hypothalamic paraventricular nucleus of rat. Brain Res 324, 91–9.

    PubMed  Article  CAS  Google Scholar 

  • Kokkotou EG, Tritos NA, Mastaitis JW, Slieker L, Maratos-Flier E (2001) Melanin-concentrating hormone receptor is a target of leptin action in the mouse brain. Endocrinology 142, 680–6.

    PubMed  Article  CAS  Google Scholar 

  • de Lecea L, Kilduff TS, Peyron C et al. (1998) The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc Natl Acad Sci USA 95, 322–7.

    PubMed  Article  Google Scholar 

  • Lee GH, Proenca R, Montez JM et al. (1996) Abnormal splicing of the leptin receptor in diabetic mice. Nature 379, 632–5.

    PubMed  Article  CAS  Google Scholar 

  • Lembo PM, Grazzini E, Cao J et al. (1999) The receptor for the orexigenic peptide melanin-concentrating hormone is a G-protein- coupled receptor. Nat Cell Biol 1, 267–71.

    PubMed  Article  CAS  Google Scholar 

  • Lin L, Faraco J, Li R et al. (1999) The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene. Cell 98, 365–76.

    PubMed  Article  CAS  Google Scholar 

  • Marshall NB, Barnett RJ, Mayer J (1955) Hypothalamic lesions in gold thioglucose injected mice. Proc Soc Exp Biol Med 90, 240–4.

    PubMed  CAS  Google Scholar 

  • McCowen KC, Chow JC, Smith RJ (1998) Leptin signaling in the hypothalamus of normal rats in vivo. Endocrinology 139, 4442–7.

    PubMed  Article  CAS  Google Scholar 

  • Mezey E, Kiss JZ, Mueller GP, Eskay R, O’Donohue TL, Palkovits M (1985) Distribution of the pro-opiomelanocortin derived peptides, adrenocorticotrope hormone, alpha-melanocyte-stimulating hormone and beta-endorphin (ACTH, alpha-MSH, beta-END) in the rat hypothalamus. Brain Res 328, 341–7.

    PubMed  Article  CAS  Google Scholar 

  • Mizuno TM, Kleopoulos SP, Bergen HT, Roberts JL, Priest CA, Mobbs CV (1998) Hypothalamic pro-opiomelanocortin mRNA is reduced by fasting in ob/ob and db/db mice, but is stimulated by leptin. Diabetes 47, 294–7.

    PubMed  Article  CAS  Google Scholar 

  • Mori M, Harada M, Terao Y et al. (2001) Cloning of a novel G protein-coupled receptor, SLT, a subtype of the melanin- concentrating hormone receptor. Biochem Biophys Res Comm 283, 1013–8.

    PubMed  Article  CAS  Google Scholar 

  • Olney JW (1969) Brain lesions, obesity, and other disturbances in mice treated with monosodium glutamate. Science 164, 719–21.

    PubMed  Article  CAS  Google Scholar 

  • Pelleymounter MA, Cullen MJ, Baker MB et al. (1995) Effects of the obese gene product on body weight regulation in ob/ob mice. Science 269, 540–3.

    PubMed  Article  CAS  Google Scholar 

  • Peyron C, Tighe DK, van den Pol AN et al. (1998) Neurons containing hypocretin (orexin) project to multiple neuronal systems. J Neurosci 18, 9996–10015.

    PubMed  CAS  Google Scholar 

  • Qu D, Ludwig DS, Gammeltoft S et al. (1996) A role for melanin- concentrating hormone in the central regulation of feeding behaviour. Nature 380, 243–7.

    PubMed  Article  CAS  Google Scholar 

  • Rossi M, Choi SJ, O’Shea D, Miyoshi T, Ghatei MA, Bloom SR (1997) Melanin-concentrating hormone acutely stimulates feeding, but chronic administration has no effect on body weight. Endocrinology 138, 351–5.

    PubMed  Article  CAS  Google Scholar 

  • Sailer AW, Sano H, Zeng Z et al. (2001) Identification and characterization of a second melanin-concentrating hormone receptor, MCH-2R. Proc Natl Acad Sci USA 98, 7564–9.

    PubMed  Article  CAS  Google Scholar 

  • Saito Y, Cheng M, Leslie FM, Civelli O (2001) Expression of the melanin-concentrating hormone (MCH) receptor mRNA in the rat brain. J Comp Neurol 435, 26–40.

    PubMed  Article  CAS  Google Scholar 

  • Saito Y, Nothacker HP, Wang Z, Lin SH, Leslie F, Civelli O (1999) Molecular characterization of the melanin-concentrating-hormone receptor. Nature 400, 265–9.

    PubMed  Article  CAS  Google Scholar 

  • Sakurai T, Amemiya A, Ishii M et al. (1998) Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 92, 573–85.

    PubMed  Article  CAS  Google Scholar 

  • Sawchenko PE (1998) Toward a new neurobiology of energy balance, appetite, and obesity: the anatomists weigh in. J Comp Neurol 402, 435–41.

    PubMed  Article  CAS  Google Scholar 

  • Schwartz MW, Woods SC, Porte D Jr, Seeley RJ, Baskin DG (2000) Central nervous system control of food intake. Nature 404, 661–71.

    PubMed  CAS  Google Scholar 

  • Shimada M, Tritos NA, Lowell BB, Flier JS, Maratos-Flier E (1998) Mice lacking melanin-concentrating hormone are hypophagic and lean. Nature 396, 670–4.

    PubMed  Article  CAS  Google Scholar 

  • Shioda S, Funahashi H, Nakajo S, Yada T, Maruta O, Nakai Y (1998) Immunohistochemical localization of leptin receptor in the rat brain. Neurosci Lett 243, 41–4.

    PubMed  Article  CAS  Google Scholar 

  • Steffens AB (1975) Influence of reversible obesity on eating behavior, blood glucose, and insulin in the rat. Am J Physiol 228, 1738–44.

    PubMed  CAS  Google Scholar 

  • Stromberg H, Svensson SP, Hermanson O (2000) Distribution of the transcription factor signal transducer and activator of transcription 3 in the rat central nervous system and dorsal root ganglia. Brain Res 853, 105–14.

    PubMed  Article  CAS  Google Scholar 

  • Tartaglia LA, Dembski M, Weng X et al. (1995) Identification and expression cloning of a leptin receptor, OB-R. Cell 83, 1263–71.

    PubMed  Article  CAS  Google Scholar 

  • Thornton JE, Cheung CC, Clifton DK, Steiner RA (1997) Regulation of hypothalamic proopiomelanocortin mRNA by leptin in ob/ob mice. Endocrinology 138, 5063–6.

    PubMed  Article  CAS  Google Scholar 

  • Tritos NA, Mastaitis JW, Kokkotou E, Maratos-Flier E (2001) Characterization of melanin concentrating hormone and preproorexin expression in the murine hypothalamus. Brain Res 895, 160–6.

    PubMed  Article  CAS  Google Scholar 

  • Vaisse C, Halaas JL, Horvath CM, Darnell JE Jr, Stoffel M, Friedman JM (1996) Leptin activation of Stat3 in the hypothalamus of wild-type and ob/ob mice but not db/db mice. Nat Genet 14, 95–7.

    PubMed  Article  CAS  Google Scholar 

  • Wang S, Behan J, O’Neill K et al. (2001) Identification and pharmacological characterization of a novel human melanin- concentrating hormone receptor, MCH-R2. J Biol Chem 276, 34 664–70.

    Article  Google Scholar 

  • Williams G, Bing C, Cai XJ, Harrold JA, King PJ, Liu XH (2001) The hypothalamus and the control of energy homeostasis: different circuits, different purposes. Physiol Behav 74, 683–701.

    PubMed  Article  CAS  Google Scholar 

  • Willie JT, Chemelli RM, Sinton CM, Yanagisawa M (2001) To eat or to sleep? Orexin in the regulation of feeding and wakefulness. Ann Rev Neurosci 24, 429–58.

    PubMed  Article  CAS  Google Scholar 

  • Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372, 425–31.

    PubMed  Article  CAS  Google Scholar 

Download references

Author information

Affiliations

  1. Department of Developmental Morphology, Tokyo Metropolitan Institute for Neuroscience, 2-6 Musashidai, Fuchu, 183-8526, Tokyo, Japan

    Hitoshi Kawano, Shizuka Honma, Akiko Honma & Masao Horie

  2. Graduate School of Sports Science, Japan Women’s College of Physical Education, Setagaya-ku, Tokyo, Japan

    Akiko Honma & Yukari Kawano

  3. Graduate School of Integrated Science, Yokohama City University, Yokohama, Kanagawa, Japan

    Shizuka Honma & Shinji Hayashi

Authors
  1. Hitoshi Kawano
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shizuka Honma
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Akiko Honma
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Masao Horie
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yukari Kawano
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shinji Hayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hitoshi Kawano.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Kawano, H., Honma, S., Honma, A. et al. Melanin-concentrating hormone neuron system: the wide web that controls the feeding. Anato Sci Int 77, 149–160 (2002). https://doi.org/10.1046/j.0022-7722.2002.00027.x

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1046/j.0022-7722.2002.00027.x

Key words

  • feeding
  • hypothalamus
  • leptin
  • melanin-concentrating hormone
  • receptor