Mice lacking the M3 muscarinic acetylcholine receptor are hypophagic and lean

Masahisa Yamada, Tsuyoshi Miyakawa, Alokesh Duttaroy, Akihiro Yamanaka, Toru Moriguchi, Ryosuke Makita, Masaharu Ogawa, Chieh J. Chou, Bing Xia, Jacqueline Crawley, Christian C. Felder, Chu Xia Deng, Jürgen Wess

Research output: Contribution to journalArticle

309 Citations (Scopus)

Abstract

Members of the muscarinic acetylcholine receptor family (M1-M5) have central roles in the regulation of many fundamental physiological functions. Identifying the specific receptor subtype(s) that mediate the diverse muscarinic actions of acetylcholine is of considerable therapeutic interest, but has proved difficult primarily because of a lack of subtype-selective ligands. Here we show that mice deficient in the M3 muscarinic receptor (M3R -/- mice) display a significant decrease in food intake, reduced body weight and peripheral fat deposits, and very low levels of serum leptin and insulin. Paradoxically, hypothalamic messenger RNA levels of melanin-concentrating hormone (MCH), which are normally upregulated in fasted animals leading to an increase in food intake, are significantly reduced in M3R -/- mice. Intra-cerebroventricular injection studies show that an agouti-related peptide analogue lacked orexigenic (appetite-stimulating) activity in M3R -/- mice. However, M3R -/- mice remained responsive to the orexigenic effects of MCH. Our data indicate that there may be a cholinergic pathway that involves M3-receptor-mediated facilitation of food intake at a site downstream of the hypothalamic leptin/melanocortin system and upstream of the MCH system.

Original languageEnglish (US)
Pages (from-to)207-212
Number of pages6
JournalNature
Volume410
Issue number6825
DOIs
StatePublished - Mar 8 2001
Externally publishedYes

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Muscarinic Receptors
Eating
Leptin
Cholinergic Agents
Muscarinic M3 Receptors
Melanocortins
Appetite
Acetylcholine
Fats
Body Weight
Insulin
Ligands
Messenger RNA
Peptides
Injections
Serum
melanin-concentrating hormone

ASJC Scopus subject areas

  • General

Cite this

Yamada, M., Miyakawa, T., Duttaroy, A., Yamanaka, A., Moriguchi, T., Makita, R., ... Wess, J. (2001). Mice lacking the M3 muscarinic acetylcholine receptor are hypophagic and lean. Nature, 410(6825), 207-212. https://doi.org/10.1038/35065604

Mice lacking the M3 muscarinic acetylcholine receptor are hypophagic and lean. / Yamada, Masahisa; Miyakawa, Tsuyoshi; Duttaroy, Alokesh; Yamanaka, Akihiro; Moriguchi, Toru; Makita, Ryosuke; Ogawa, Masaharu; Chou, Chieh J.; Xia, Bing; Crawley, Jacqueline; Felder, Christian C.; Deng, Chu Xia; Wess, Jürgen.

In: Nature, Vol. 410, No. 6825, 08.03.2001, p. 207-212.

Research output: Contribution to journalArticle

Yamada, M, Miyakawa, T, Duttaroy, A, Yamanaka, A, Moriguchi, T, Makita, R, Ogawa, M, Chou, CJ, Xia, B, Crawley, J, Felder, CC, Deng, CX & Wess, J 2001, 'Mice lacking the M3 muscarinic acetylcholine receptor are hypophagic and lean', Nature, vol. 410, no. 6825, pp. 207-212. https://doi.org/10.1038/35065604
Yamada M, Miyakawa T, Duttaroy A, Yamanaka A, Moriguchi T, Makita R et al. Mice lacking the M3 muscarinic acetylcholine receptor are hypophagic and lean. Nature. 2001 Mar 8;410(6825):207-212. https://doi.org/10.1038/35065604
Yamada, Masahisa ; Miyakawa, Tsuyoshi ; Duttaroy, Alokesh ; Yamanaka, Akihiro ; Moriguchi, Toru ; Makita, Ryosuke ; Ogawa, Masaharu ; Chou, Chieh J. ; Xia, Bing ; Crawley, Jacqueline ; Felder, Christian C. ; Deng, Chu Xia ; Wess, Jürgen. / Mice lacking the M3 muscarinic acetylcholine receptor are hypophagic and lean. In: Nature. 2001 ; Vol. 410, No. 6825. pp. 207-212.
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