Abstract | BACKGROUND AND PURPOSE: EXPERIMENTAL APPROACH: To examine the mechanisms of action of the anti- obesity effect of MCH1 receptor antagonists more precisely, we conducted a pair-feeding study in mice with diet-induced obesity (DIO), chronically treated with an orally active and highly selective MCH1 receptor antagonist and examined changes in mRNA expression levels in liver, brown and white adipose tissues. We also assessed the acute effects of the MCH1 receptor antagonist in energy expenditure under thermoneutral conditions. KEY RESULTS: Treatment with the MCH1 receptor antagonist at 30 mg.kg(-1) for 1 month moderately suppressed feeding and significantly reduced body weight by 24%. In contrast, pair-feeding resulted in a smaller weight reduction of 10%. Treatment with the MCH1 receptor antagonist resulted in a higher body temperature compared with the pair-fed group. TaqMan and calorimetry data suggested that the MCH1 receptor antagonist also stimulated thermogenesis. CONCLUSIONS AND IMPLICATIONS: Our results indicate that an MCH1 receptor antagonist caused anti- obesity effects im mice by acting on both energy intake and energy expenditure.
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Authors | Masahiko Ito, A Ishihara, A Gomori, H Matsushita, Makoto Ito, J M Metzger, D J Marsh, Y Haga, H Iwaasa, S Tokita, N Takenaga, N Sato, D J MacNeil, M Moriya, A Kanatani |
Journal | British journal of pharmacology
(Br J Pharmacol)
Vol. 159
Issue 2
Pg. 374-83
(Jan 01 2010)
ISSN: 1476-5381 [Electronic] England |
PMID | 20015294
(Publication Type: Journal Article)
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Chemical References |
- 4-(benzyloxy)-1-(4-(2-pyrrolidin-1-ylethoxy)phenyl)pyridin-2(3H)-one
- Anti-Obesity Agents
- MCHR1 protein, human
- Pyridones
- Pyrrolidines
- RNA, Messenger
- Receptors, Somatostatin
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Topics |
- Adipose Tissue, Brown
(drug effects, metabolism)
- Adipose Tissue, White
(drug effects, metabolism)
- Animals
- Anti-Obesity Agents
(pharmacokinetics, pharmacology)
- CHO Cells
- Cricetinae
- Cricetulus
- Eating
(drug effects)
- Energy Metabolism
(drug effects)
- Humans
- Liver
(drug effects, metabolism)
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Pyridones
(pharmacokinetics, pharmacology)
- Pyrrolidines
(pharmacokinetics, pharmacology)
- RNA, Messenger
(biosynthesis)
- Radioligand Assay
- Rats
- Receptors, Somatostatin
(antagonists & inhibitors, biosynthesis, genetics)
- Thermogenesis
(drug effects)
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