Anti-obesity effect of SR141716, a CB1 receptor antagonist, in diet-induced obese mice
Central Nervous System Research, Sanofi-Synthélabo, 31036 Toulouse Cedex, France Because the CB1 receptor antagonist SR141716 was previously reported to modulate food intake in rodents, we studied its efficacy in reducing obesity in a diet-induced obesity (DIO) model widely used for research on the...
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| Veröffentlicht in: | American journal of physiology. Regulatory, integrative and comparative physiology integrative and comparative physiology, 2003-02, Vol.284 (2), p.345-R353 |
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| container_title | American journal of physiology. Regulatory, integrative and comparative physiology |
| container_volume | 284 |
| creator | Ravinet Trillou, Christine Arnone, Michele Delgorge, Claire Gonalons, Nadine Keane, Peter Maffrand, Jean-Pierre Soubrie, Philippe |
| description | Central Nervous System Research, Sanofi-Synthélabo,
31036 Toulouse Cedex, France
Because the CB1 receptor antagonist
SR141716 was previously reported to modulate food intake in rodents, we
studied its efficacy in reducing obesity in a diet-induced obesity
(DIO) model widely used for research on the human obesity syndrome.
During a 5-wk treatment, SR141716 (10 mg · kg 1 · day 1
orally) induced a transient reduction of food intake ( 48% on week 1 ) and a marked but sustained reduction of body weight
( 20%) and adiposity ( 50%) of DIO mice. Furthermore, SR141716
corrected the insulin resistance and lowered plasma leptin, insulin,
and free fatty acid levels. Most of these effects were present, but less pronounced at 3 mg · kg 1 · day 1 .
In addition to its hypophagic action, SR141716 may influence metabolic
processes as the body weight loss of SR141716-treated mice was
significantly higher during 24-h fasting compared with vehicle-treated
animals, and when a 3-day treatment was compared with a pair feeding.
SR141716 had no effect in CB1 receptor knockout mice, which confirmed
the implication of CB1 receptors in the activity of the compound. These
findings suggest that SR141716 has a potential as a novel anti-obesity treatment.
endocannabinoid; body weight; food intake; insulin resistance; metabolic rate; CB1 receptor knockout mice |
| doi_str_mv | 10.1152/ajpregu.00545.2002 |
| format | Article |
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31036 Toulouse Cedex, France
Because the CB1 receptor antagonist
SR141716 was previously reported to modulate food intake in rodents, we
studied its efficacy in reducing obesity in a diet-induced obesity
(DIO) model widely used for research on the human obesity syndrome.
During a 5-wk treatment, SR141716 (10 mg · kg 1 · day 1
orally) induced a transient reduction of food intake ( 48% on week 1 ) and a marked but sustained reduction of body weight
( 20%) and adiposity ( 50%) of DIO mice. Furthermore, SR141716
corrected the insulin resistance and lowered plasma leptin, insulin,
and free fatty acid levels. Most of these effects were present, but less pronounced at 3 mg · kg 1 · day 1 .
In addition to its hypophagic action, SR141716 may influence metabolic
processes as the body weight loss of SR141716-treated mice was
significantly higher during 24-h fasting compared with vehicle-treated
animals, and when a 3-day treatment was compared with a pair feeding.
SR141716 had no effect in CB1 receptor knockout mice, which confirmed
the implication of CB1 receptors in the activity of the compound. These
findings suggest that SR141716 has a potential as a novel anti-obesity treatment.
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31036 Toulouse Cedex, France
Because the CB1 receptor antagonist
SR141716 was previously reported to modulate food intake in rodents, we
studied its efficacy in reducing obesity in a diet-induced obesity
(DIO) model widely used for research on the human obesity syndrome.
During a 5-wk treatment, SR141716 (10 mg · kg 1 · day 1
orally) induced a transient reduction of food intake ( 48% on week 1 ) and a marked but sustained reduction of body weight
( 20%) and adiposity ( 50%) of DIO mice. Furthermore, SR141716
corrected the insulin resistance and lowered plasma leptin, insulin,
and free fatty acid levels. Most of these effects were present, but less pronounced at 3 mg · kg 1 · day 1 .
In addition to its hypophagic action, SR141716 may influence metabolic
processes as the body weight loss of SR141716-treated mice was
significantly higher during 24-h fasting compared with vehicle-treated
animals, and when a 3-day treatment was compared with a pair feeding.
SR141716 had no effect in CB1 receptor knockout mice, which confirmed
the implication of CB1 receptors in the activity of the compound. These
findings suggest that SR141716 has a potential as a novel anti-obesity treatment.
endocannabinoid; body weight; food intake; insulin resistance; metabolic rate; CB1 receptor knockout mice</description><subject>Animals</subject><subject>Binding Sites</subject><subject>Body Weight - drug effects</subject><subject>Diet</subject><subject>Dietary Fats - administration & dosage</subject><subject>Dietary Fats - pharmacology</subject><subject>Dose-Response Relationship, Drug</subject><subject>Fatty Acids, Nonesterified - blood</subject><subject>Insulin - blood</subject><subject>Leptin - blood</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Obesity - blood</subject><subject>Obesity - chemically induced</subject><subject>Obesity - drug therapy</subject><subject>Obesity - physiopathology</subject><subject>Piperidines - pharmacology</subject><subject>Piperidines - therapeutic use</subject><subject>Pyrazoles - pharmacology</subject><subject>Pyrazoles - therapeutic use</subject><subject>Receptors, Cannabinoid</subject><subject>Receptors, Drug - antagonists & inhibitors</subject><subject>Receptors, Drug - genetics</subject><subject>Receptors, Drug - metabolism</subject><subject>Time Factors</subject><issn>0363-6119</issn><issn>1522-1490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kF1PwjAUhhujEUT_gBemP4Bhe9p99BKJqAmJCaK3TdlOR8nYlq1E-fcOgXDl1cnJeZ83Jw8h95yNOA_h0azrBvPtiLFQhiNgDC5IvztAwKVil6TPRCSCiHPVIzdtu2aMSSHFNelxEEpBCH3yNS69C6olts7vKFqLqaeVpR9zLnnMoyE1dPLEaYMp1r5qqCm9yavStX5IXUkzhz5wZbZNMaP7GqQbl-ItubKmaPHuOAfkc_q8mLwGs_eXt8l4FqQiiX2AS5lESZxEyiqBAmIhbaoUSwQDptIoWoahik1mo1hxBsLE3Qog0VgACEMxIHDoTZuqbRu0um7cxjQ7zZneS9JHSfpPkt5L6qCHA1RvlxvMzsjRShdQh8DK5atv16CuV7vWVUWV7_R0WxQL_PGnZkikBj0XXXud2Y4N_mdPz5wZ8QtLZ4Zm</recordid><startdate>20030201</startdate><enddate>20030201</enddate><creator>Ravinet Trillou, Christine</creator><creator>Arnone, Michele</creator><creator>Delgorge, Claire</creator><creator>Gonalons, Nadine</creator><creator>Keane, Peter</creator><creator>Maffrand, Jean-Pierre</creator><creator>Soubrie, Philippe</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>20030201</creationdate><title>Anti-obesity effect of SR141716, a CB1 receptor antagonist, in diet-induced obese mice</title><author>Ravinet Trillou, Christine ; Arnone, Michele ; Delgorge, Claire ; Gonalons, Nadine ; Keane, Peter ; Maffrand, Jean-Pierre ; Soubrie, Philippe</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c387t-eb48687869f93e32734fc990830209c66b5597adf6791023a7597224eaf222553</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Animals</topic><topic>Binding Sites</topic><topic>Body Weight - drug effects</topic><topic>Diet</topic><topic>Dietary Fats - administration & dosage</topic><topic>Dietary Fats - pharmacology</topic><topic>Dose-Response Relationship, Drug</topic><topic>Fatty Acids, Nonesterified - blood</topic><topic>Insulin - blood</topic><topic>Leptin - blood</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Obesity - blood</topic><topic>Obesity - chemically induced</topic><topic>Obesity - drug therapy</topic><topic>Obesity - physiopathology</topic><topic>Piperidines - pharmacology</topic><topic>Piperidines - therapeutic use</topic><topic>Pyrazoles - pharmacology</topic><topic>Pyrazoles - therapeutic use</topic><topic>Receptors, Cannabinoid</topic><topic>Receptors, Drug - antagonists & inhibitors</topic><topic>Receptors, Drug - genetics</topic><topic>Receptors, Drug - metabolism</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ravinet Trillou, Christine</creatorcontrib><creatorcontrib>Arnone, Michele</creatorcontrib><creatorcontrib>Delgorge, Claire</creatorcontrib><creatorcontrib>Gonalons, Nadine</creatorcontrib><creatorcontrib>Keane, Peter</creatorcontrib><creatorcontrib>Maffrand, Jean-Pierre</creatorcontrib><creatorcontrib>Soubrie, Philippe</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>American journal of physiology. 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31036 Toulouse Cedex, France
Because the CB1 receptor antagonist
SR141716 was previously reported to modulate food intake in rodents, we
studied its efficacy in reducing obesity in a diet-induced obesity
(DIO) model widely used for research on the human obesity syndrome.
During a 5-wk treatment, SR141716 (10 mg · kg 1 · day 1
orally) induced a transient reduction of food intake ( 48% on week 1 ) and a marked but sustained reduction of body weight
( 20%) and adiposity ( 50%) of DIO mice. Furthermore, SR141716
corrected the insulin resistance and lowered plasma leptin, insulin,
and free fatty acid levels. Most of these effects were present, but less pronounced at 3 mg · kg 1 · day 1 .
In addition to its hypophagic action, SR141716 may influence metabolic
processes as the body weight loss of SR141716-treated mice was
significantly higher during 24-h fasting compared with vehicle-treated
animals, and when a 3-day treatment was compared with a pair feeding.
SR141716 had no effect in CB1 receptor knockout mice, which confirmed
the implication of CB1 receptors in the activity of the compound. These
findings suggest that SR141716 has a potential as a novel anti-obesity treatment.
endocannabinoid; body weight; food intake; insulin resistance; metabolic rate; CB1 receptor knockout mice</abstract><cop>United States</cop><pmid>12399252</pmid><doi>10.1152/ajpregu.00545.2002</doi></addata></record> |
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| source | MEDLINE; American Physiological Society; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Animals Binding Sites Body Weight - drug effects Diet Dietary Fats - administration & dosage Dietary Fats - pharmacology Dose-Response Relationship, Drug Fatty Acids, Nonesterified - blood Insulin - blood Leptin - blood Male Mice Mice, Inbred C57BL Mice, Knockout Obesity - blood Obesity - chemically induced Obesity - drug therapy Obesity - physiopathology Piperidines - pharmacology Piperidines - therapeutic use Pyrazoles - pharmacology Pyrazoles - therapeutic use Receptors, Cannabinoid Receptors, Drug - antagonists & inhibitors Receptors, Drug - genetics Receptors, Drug - metabolism Time Factors |
| title | Anti-obesity effect of SR141716, a CB1 receptor antagonist, in diet-induced obese mice |
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