Antiobesity Effect of a Melanin-Concentrating Hormone 1 Receptor Antagonist in Diet-Induced Obese Mice

Mashiko, Satoshi; Ishihara, Akane; Gomori, Akira; Moriya, Ryuichi; Ito, Makoto; Iwaasa, Hisashi; Matsuda, Masao; Feng, Yue; Shen, Zhu; Marsh, Donald J.; Bednarek, Maria A.; MacNeil, Douglas J.; Kanatani, Akio

doi:10.1210/en.2004-1150

Cited by 73 publications

(64 citation statements)

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“…In Experiment 1b, a 42% fat diet (Medium high fat-MHF-diet, Purified High Fat diet with lard, 4031.09, Arie Block BV, Woerden, The Netherlands; 4.7 kcal/g) was also used. [18]. The antagonist peptide was shown to exhibit a high affinity for the MCH1-R with a K i value of 9.9 nM.…”

Section: Animals and Dietsmentioning

confidence: 96%

“…The antagonist peptide was shown to exhibit a high affinity for the MCH1-R with a K i value of 9.9 nM. It showed an antagonistic activity in a functional assay with an IC50 value of 15 nM [18]. Rats were injected with either saline (4 Al), MCH (5 Ag in 4 Al saline), MCH and the MCH1-R antagonist (5 Ag + 10 Ag, respectively, in 4 Al saline) or the MCH1-R antagonist alone (10 Ag in 4 Al of saline) through an injector ending 1 mm lower than the guide cannula.…”

Section: Animals and Dietsmentioning

confidence: 99%

“…In the recent years, several MCH1-R antagonists such as T-226296 [27], SNAP-7941 [4] or the antagonist characterized by Bednarek et al [1], Shearman et al [23] and Mashiko et al [18] have been developed. These drugs significantly reduce MCH-induced increase in food intake when MCH is injected centrally and the antagonist is given orally (T-226296, [27]), intraperitoneally (SNAP-7941, [4]) or intracerebroventrically [18,23].…”

Section: Introductionmentioning

confidence: 99%

“…These drugs significantly reduce MCH-induced increase in food intake when MCH is injected centrally and the antagonist is given orally (T-226296, [27]), intraperitoneally (SNAP-7941, [4]) or intracerebroventrically [18,23].…”

Section: Introductionmentioning

confidence: 99%

“…Chronic treatment with an MCH1-R antagonist alters appetite, body weight and adiposity in Sprague -Dawley rats [23] and in diet-induced obese (DIO) mice [18]. In addition, Borowsky et al [4] showed that the MCH1-R antagonist SNAP-7941 injected intraperitoneally would block the intake a highly palatable food (sweet condensed milk).…”

Section: Introductionmentioning

confidence: 99%

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Effects of MCH and a MCH1-receptor antagonist on (palatable) food and water intake

Morens

Nørregaard²,

Receveur³

et al. 2005

Brain Research

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Receveur, J-M. (2005). Effects of MCH and a MCH1-receptor antagonist on (palatable) food and water intake. Brain-research, 1062(1-2), 32-38. DOI: 10.1016DOI: 10. /j.brainres.2005 Copyright Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum. AbstractMelanin concentrating hormone (MCH) is a regulator of ingestive behavior, but several issues regarding its effects on specific components of ingestive behavior remain to be elucidated. Therefore, we injected, in the 3rd ventricle of male Wistar rats, saline, MCH (5 Ag), MCH (5 Ag) together with a MCH1-R antagonist (A, 10 Ag) and the antagonist alone (A, 10 Ag). Our results show that (1) central administration of MCH stimulates food intake (lab chow and medium high fat diet) and this can be blocked by a MCH1-R antagonist; (2) the MCH-induced increase in food intake is mediated through increased meal number, meal duration and meal size; (3) the MCH1-R antagonist is able to significantly reduce the intake of a highly palatable food (condensed sweet milk) and is more effective in blocking MCH-induced food intake when rats are fed a palatable medium high fat food; and (4) MCH stimulated water intake independently from and disproportionately to food intake. In conclusion, our results point to an involvement of endogenous MCH in the enhanced intake of palatable food. Furthermore, they confirm that MCH stimulates not only food intake but also water intake. D

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Section: Animals and Dietsmentioning

confidence: 96%

Section: Animals and Dietsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Effects of MCH and a MCH1-receptor antagonist on (palatable) food and water intake

Morens

Nørregaard²,

Receveur³

et al. 2005

Brain Research

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Antiobesity Pharmacotherapy: Current Treatment Options and Future Perspectives

Shi

2007

Handbook of Contemporary Neuropharmacology

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This chapter provides a summary of historic perspectives and currently available pharmaceutical therapies for the treatment of obesity. An overview is provided on the pipeline of anti‐obesity drugs currently in development; with emphasis on the central mechanisms of these drug candidates. The obesity drug market has encountered frequent problems in the past with limited efficacy, toxicity, and strong resistance of the system to perturbation. These hurdles can be overcome in the future with progress in our understanding of the complicated and often redundant pathways that safeguards the energy metabolism for survival under both feast and famine conditions. To be ultimately successful, obesity treatments may require combination therapies that target both central and peripheral mechanisms as well as behavior modifications to achieve sustained weight loss effect.

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Neurochemical characterization of neurons expressing melanin‐concentrating hormone receptor 1 in the mouse hypothalamus

Chee

Pissios

Maratos–Flier

2013

J of Comparative Neurology

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Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide that acts via MCH receptor 1 (MCHR1) in the mouse. It promotes positive energy balance thus mice lacking MCH or MCHR1 are lean, hyperactive, and resistant to diet-induced obesity. Identifying the cellular targets of MCH is an important step to understanding the mechanisms underlying MCH actions. We generated the Mchr1-cre mouse that expressed cre recombinase driven by the MCHR1 promoter and crossed it with a tdTomato reporter mouse. The resulting Mchr1-cre/tdTomato progeny expressed easily detectable tdTomato fluorescence in MCHR1 neurons, which were found throughout the olfactory system, striatum, and hypothalamus. To chemically identify MCH-targeted cell populations that play a role in energy balance, MCHR1 hypothalamic neurons were characterized by colabeling select hypothalamic neuropeptides with tdTomato fluorescence. TdTomato fluorescence colocalized with dynorphin, oxytocin, vasopressin, enkephalin, thyrothropin-releasing hormone, and corticotropin-releasing factor immunoreactive cells in the paraventricular nucleus. In the lateral hypothalamus, neurotensin but neither orexin nor MCH neurons expressed tdTomato. In the arcuate nucleus, both Neuropeptide Y and proopiomelanocortin cells expressed tdTomato. We further demonstrated that some of these arcuate neurons were also targets of leptin action. Interestingly, MCHR1 was expressed in the vast majority of leptin-sensitive proopiomelanocortin neurons, highlighting their importance for the orexigenic actions of MCH. Taken together, this study supports the use of the Mchr1-cre mouse for outlining the neuroanatomical distribution and neurochemical phenotype of MCHR1 neurons.

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Antiobesity Effect of a Melanin-Concentrating Hormone 1 Receptor Antagonist in Diet-Induced Obese Mice

Cited by 73 publications

References 28 publications

Effects of MCH and a MCH1-receptor antagonist on (palatable) food and water intake

Effects of MCH and a MCH1-receptor antagonist on (palatable) food and water intake

Antiobesity Pharmacotherapy: Current Treatment Options and Future Perspectives

Neurochemical characterization of neurons expressing melanin‐concentrating hormone receptor 1 in the mouse hypothalamus

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