Review MCH and feeding behavior-interaction with peptidic network B. Griffond, P.Y. Risold * EA3922, Universite ´ de Franche-Comte ´, Faculte ´ de Me ´decine et de Pharmacie, 19 rue Ambroise Pare ´, 25000 Besanc ¸on, France Contents 1. Experimental data ............................................................................................... 2045 2. MCH neurons and control of energy homeostasis ...................................................................... 2046 2.1. Histological and experimental data underlying (or not) MCH position in the hypothalamic loop regulating food intake ........ 2047 2.1.1. MCH and a-MSH ................................................................................... 2047 2.1.2. MCH and CART .................................................................................... 2047 2.1.3. MCH and NPY ..................................................................................... 2047 2.1.4. MCH and AgRP..................................................................................... 2047 2.1.5. MCH and Hcrt ..................................................................................... 2048 2.2. Anatomical data ........................................................................................... 2048 3. Conclusions .................................................................................................... 2048 References ..................................................................................................... 2049 When we think MCH (melanin-concentrating hormone), we think feeding behavior. This is now a reflex, but it is true that a rapid look to the bibliographical record shows how much this topic has been covered by researchers. Many reviews have been published in which the experimental data concerning the implication of MCH and Hcrt (hypocretin/orexin) neurons in energy balance are summarized (for example [3,28,32,34,42,48,52,62,67,77,98,99,120]). However, when reading the literature, it is apparent that although the experimental data is abundant, little is known about the exact mechanisms through which MCH neurons could act. It is suggested that MCH acts in concert with other neuropeptides, including Hcrt produced by neighboring neurons, and NPY (neuropeptide Y) or POMC (pro-opiomelanocortin) in neurons of the arcuate nucleus. But others may be involved. In this review, after a rapid overview of the experimental data, we shall attempt to make a synthesis of what is known about the MCH interaction with other peptides and their receptors, and about the mechanisms and circuit that may relate the MCH system to the feeding behavior and energy homeostasis. 1. Experimental data The dualistic ‘‘feeding and satiety centers’’ hypothesis estab- lished during the 1950s [5,105] led, 40 years later, many authors to envisage a role of MCH in the central regulation of food intake in mammals because of the striking localization of MCH neurons in the Peptides 30 (2009) 2045–2051 ARTICLE INFO Article history: Received 26 January 2009 Received in revised form 17 April 2009 Accepted 9 July 2009 Available online 18 July 2009 Keywords: MCH NPY POMC Hypocretin Hypothalamus ABSTRACT Numerous works associate the MCH peptide, and the hypothalamic neurons that produce it, to the feeding behavior and energy homeostasis. It is commonly admitted that MCH is an orexigenic peptide, and MCH neurons could be under the control of arcuate NPY and POMC neurons. However, the literature data is not always concordant. In particular questions about the intrahypothalamic circuit involving other neuropeptides and about the mechanisms through which MCH could act are not yet clearly answered. For example, which receptors mediate a MCH response to NPY or alpha-MSH, does MCH act alone, is there any local anatomical organization within the tuberal LHA? A review of the current literature is then needed to help focus attention on these unresolved and often neglected issues. ß 2009 Elsevier Inc. All rights reserved. * Corresponding author. Tel.: +33 363 08 22 23; fax: +33 363 08 22 80. E-mail address: pierre-yves.risold@univ-fcomte.fr (P.Y. Risold). Contents lists available at ScienceDirect Peptides journal homepage: www.elsevier.com/locate/peptides 0196-9781/$ – see front matter ß 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.peptides.2009.07.008