Metabotropic glutamate receptor mGlu5 is a mediator of appetite and energy balance in rats and mice. Export

@article{citeulike:4785482, abstract = {The metabotropic glutamate receptor subtype mGlu5 modulates central reward pathways. Many transmitter systems within reward pathways affect feeding. We examined the potential role of mGlu5 in body weight regulation using genetic and pharmacological approaches. Adult mice lacking mGlu5, mGluR5-/-, weighed significantly less than littermate controls (mGluR5+/+, despite no difference in ad libitum food intake. After overnight food deprivation, mGluR5-/- mice ate significantly less than their mGluR5+/+ controls when refeeding. When on a high fat diet, mGluR5-/- mice weighed less and had decreased plasma insulin and leptin concentrations. The selective mGlu5 antagonist MTEP [3-[(2-methyl-1,3-thiazol-4-yl)-ethynyl]-pyridine; 15 mg/kg s.c.] reduced refeeding after overnight food deprivation in mGluR5+/+, but not mGluR5-/- mice, demonstrating that feeding suppression is mediated via a mGlu5 mechanism. MTEP (1-10 mg/kg) decreased night-time food intake in rats in a dose-related manner. At 10 mg/kg, MTEP injected at 8.5, 4.5, or 0.5 h before refeeding reduced overnight food intake by approximately approximately 30\%. Diet-induced obese (DIO) and age-matched lean rats were treated for 12 days with MTEP (3 or 10 mg/kg/day s.c.), dexfenfluramine (3 mg/kg/day s.c.), or vehicle. Daily and cumulative food intakes were reduced in DIO rats by MTEP and dexfenfluramine. Weight gain was prevented with MTEP (3 mg/kg), and weight and adiposity loss was seen with MTEP (10 mg/kg) and dexfenfluramine. Caloric efficiency was decreased, suggesting increased energy expenditure. In lean rats, similar, although smaller, effects were observed. In conclusion, using genetic and pharmacological approaches, we have shown that mGlu5 modulates food intake and energy balance in rodents.}, author = {Bradbury, M. J. and Campbell, U. and Giracello, D. and Chapman, D. and King, C. and Tehrani, L. and Cosford, N. D. and Anderson, J. and Varney, M. A. and Strack, A. M.}, citeulike-article-id = {4785482}, citeulike-linkout-0 = {http://dx.doi.org/10.1124/jpet.104.076406}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/15590770}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=15590770}, comment = {Bradbury 2009 mGluR5 responsible for leaner mice and rats * lighter (ca. 10\%) * slower weight gain (ca. 50\%) * eat less after food deprivation * lowered leptin and insulin plasma levels when on high fat diet * MTEP reduce food intake by 30\% mechanism not sure * (metabolic change, reward properties of food less likely aversion to MTEP) MTEP * kinetics: 3mg/kg in minutes 100\% occupancy, in 4h 0\% (Anderson, 2003) * tolerance: observed at high doses Hypothalamus * lateral hypothalamic area - main integration are for reward and metabolic information (Kalra, 1999) * PVN - interaction of CB1 with mGluR5 shown (Kelley and Berridge, 2002) * Subparaventricular nucleus - high expression of mGluR5 }, doi = {10.1124/jpet.104.076406}, issn = {0022-3565}, journal = {The Journal of pharmacology and experimental therapeutics}, keywords = {ko, metabolism, mglur5, mtep, obesity, reward, weight}, month = {April}, number = {1}, pages = {395--402}, posted-at = {2009-06-09 11:21:14}, priority = {0}, title = {Metabotropic glutamate receptor mGlu5 is a mediator of appetite and energy balance in rats and mice.}, url = {http://dx.doi.org/10.1124/jpet.104.076406}, volume = {313}, year = {2005} }

TY - JOUR ID - citeulike:4785482 L3 - citeulike-article-id:4785482 N2 - The metabotropic glutamate receptor subtype mGlu5 modulates central reward pathways. Many transmitter systems within reward pathways affect feeding. We examined the potential role of mGlu5 in body weight regulation using genetic and pharmacological approaches. Adult mice lacking mGlu5, mGluR5-/-, weighed significantly less than littermate controls (mGluR5+/+, despite no difference in ad libitum food intake. After overnight food deprivation, mGluR5-/- mice ate significantly less than their mGluR5+/+ controls when refeeding. When on a high fat diet, mGluR5-/- mice weighed less and had decreased plasma insulin and leptin concentrations. The selective mGlu5 antagonist MTEP [3-[(2-methyl-1,3-thiazol-4-yl)-ethynyl]-pyridine; 15 mg/kg s.c.] reduced refeeding after overnight food deprivation in mGluR5+/+, but not mGluR5-/- mice, demonstrating that feeding suppression is mediated via a mGlu5 mechanism. MTEP (1-10 mg/kg) decreased night-time food intake in rats in a dose-related manner. At 10 mg/kg, MTEP injected at 8.5, 4.5, or 0.5 h before refeeding reduced overnight food intake by approximately approximately 30%. Diet-induced obese (DIO) and age-matched lean rats were treated for 12 days with MTEP (3 or 10 mg/kg/day s.c.), dexfenfluramine (3 mg/kg/day s.c.), or vehicle. Daily and cumulative food intakes were reduced in DIO rats by MTEP and dexfenfluramine. Weight gain was prevented with MTEP (3 mg/kg), and weight and adiposity loss was seen with MTEP (10 mg/kg) and dexfenfluramine. Caloric efficiency was decreased, suggesting increased energy expenditure. In lean rats, similar, although smaller, effects were observed. In conclusion, using genetic and pharmacological approaches, we have shown that mGlu5 modulates food intake and energy balance in rodents. IS - 1 JF - The Journal of pharmacology and experimental therapeutics SN - 0022-3565 EP - 402 TI - Metabotropic glutamate receptor mGlu5 is a mediator of appetite and energy balance in rats and mice. VL - 313 SP - 395 KW - ko KW - metabolism KW - mglur5 KW - mtep KW - obesity KW - reward KW - weight N1 - Bradbury 2009 mGluR5 responsible for leaner mice and rats * lighter (ca. 10%) * slower weight gain (ca. 50%) * eat less after food deprivation * lowered leptin and insulin plasma levels when on high fat diet * MTEP reduce food intake by 30% mechanism not sure * (metabolic change, reward properties of food less likely aversion to MTEP) MTEP * kinetics: 3mg/kg in minutes 100% occupancy, in 4h 0% (Anderson, 2003) * tolerance: observed at high doses Hypothalamus * lateral hypothalamic area - main integration are for reward and metabolic information (Kalra, 1999) * PVN - interaction of CB1 with mGluR5 shown (Kelley and Berridge, 2002) * Subparaventricular nucleus - high expression of mGluR5 AU - Bradbury, MJ AU - Campbell, U AU - Giracello, D AU - Chapman, D AU - King, C AU - Tehrani, L AU - Cosford, ND AU - Anderson, J AU - Varney, MA AU - Strack, AM PY - 2005/04// UR - http://dx.doi.org/10.1124/jpet.104.076406 ER -