Effects of a selective melanin-concentrating hormone 1 receptor antagonist on food intake and energy homeostasis in diet-induced obese mice
Melanin concentrating hormone (MCH) is a cyclic neuropeptide expressed in the lateral hypothalamus that plays an important role in energy homeostasis. To investigate the pharmacological consequences of inhibiting MCH signaling in murine obesity models, we examined the effect of acute and chronic adm...
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| Veröffentlicht in: | European journal of pharmacology 2006-03, Vol.535 (1), p.182-191 |
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| creator | Kowalski, Timothy J. Spar, Brian D. Weig, Blair Farley, Constance Cook, John Ghibaudi, Lorraine Fried, Steve O'Neill, Kim Del Vecchio, Robert A. McBriar, Mark Guzik, Henry Clader, John Hawes, Brian E. Hwa, Joyce |
| description | Melanin concentrating hormone (MCH) is a cyclic neuropeptide expressed in the lateral hypothalamus that plays an important role in energy homeostasis. To investigate the pharmacological consequences of inhibiting MCH signaling in murine obesity models, we examined the effect of acute and chronic administration of a selective MCH1 receptor antagonist (SCH-A) in diet-induced obese (DIO) and
Lep
ob/ob
mice. Oral administration of SCH-A for 5 consecutive days (30 mg/kg q.d.) produced hypophagia, a loss of body weight and adiposity, and decreased plasma leptin levels in DIO mice, and hypophagia and reduced weight gain in
Lep
ob/ob
mice. Chronic administration of SCH-A to DIO mice decreased food intake, body weight and adiposity, and plasma leptin and free fatty acids. These effects were accompanied by increases in several hypothalamic neuropeptides. Acute administration of SCH-A (30 mg/kg) prevented the decrease in energy expenditure associated with food restriction. These results indicate that MCH1 receptor antagonists may be effective in the treatment of obesity. |
| doi_str_mv | 10.1016/j.ejphar.2006.01.062 |
| format | Article |
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Lep
ob/ob
mice. Oral administration of SCH-A for 5 consecutive days (30 mg/kg q.d.) produced hypophagia, a loss of body weight and adiposity, and decreased plasma leptin levels in DIO mice, and hypophagia and reduced weight gain in
Lep
ob/ob
mice. Chronic administration of SCH-A to DIO mice decreased food intake, body weight and adiposity, and plasma leptin and free fatty acids. These effects were accompanied by increases in several hypothalamic neuropeptides. Acute administration of SCH-A (30 mg/kg) prevented the decrease in energy expenditure associated with food restriction. These results indicate that MCH1 receptor antagonists may be effective in the treatment of obesity.</description><identifier>ISSN: 0014-2999</identifier><identifier>EISSN: 1879-0712</identifier><identifier>DOI: 10.1016/j.ejphar.2006.01.062</identifier><identifier>PMID: 16540104</identifier><identifier>CODEN: EJPHAZ</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject><![CDATA[Adipose Tissue - drug effects ; Administration, Oral ; Animals ; Binding, Competitive ; Biological and medical sciences ; Body Weight - drug effects ; Brain - metabolism ; CHO Cells ; Cricetinae ; Cricetulus ; Dietary Fats - administration & dosage ; Dose-Response Relationship, Drug ; Eating - drug effects ; Energy Metabolism - drug effects ; Fatty Acids, Nonesterified - blood ; Female ; Galanin - genetics ; Gene Expression - drug effects ; Homeostasis - drug effects ; Hypothalamic Hormones - genetics ; Hypothalamus - drug effects ; Hypothalamus - metabolism ; Indirect calorimetry ; Insulin - blood ; Intracellular Signaling Peptides and Proteins - genetics ; Iodine Radioisotopes ; Leptin - blood ; Male ; Medical sciences ; Melanin-concentrating hormone ; Melanins - genetics ; Metabolic diseases ; Mice ; Mice, Inbred C57BL ; Mice, Obese ; Neuropeptide Y - genetics ; Neuropeptides - genetics ; Nitriles - administration & dosage ; Nitriles - pharmacology ; Obesity ; Obesity - etiology ; Obesity - physiopathology ; Oligopeptides - metabolism ; Orexin Receptors ; Orexins ; Pharmacology. Drug treatments ; Piperazines - administration & dosage ; Piperazines - pharmacology ; Pituitary Hormones - genetics ; Protein Binding ; Receptor antagonist ; Receptors, G-Protein-Coupled ; Receptors, Neuropeptide ; Receptors, Somatostatin - antagonists & inhibitors ; Receptors, Somatostatin - genetics ; Receptors, Somatostatin - metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Triglycerides - blood ; Urea - administration & dosage ; Urea - analogs & derivatives ; Urea - pharmacology]]></subject><ispartof>European journal of pharmacology, 2006-03, Vol.535 (1), p.182-191</ispartof><rights>2006 Elsevier B.V.</rights><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c421t-13f081830a416fe8381715b57b83dd887733fb74c435aff801f63e81f7576ffd3</citedby><cites>FETCH-LOGICAL-c421t-13f081830a416fe8381715b57b83dd887733fb74c435aff801f63e81f7576ffd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ejphar.2006.01.062$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,782,786,3552,27931,27932,46002</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17630090$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16540104$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kowalski, Timothy J.</creatorcontrib><creatorcontrib>Spar, Brian D.</creatorcontrib><creatorcontrib>Weig, Blair</creatorcontrib><creatorcontrib>Farley, Constance</creatorcontrib><creatorcontrib>Cook, John</creatorcontrib><creatorcontrib>Ghibaudi, Lorraine</creatorcontrib><creatorcontrib>Fried, Steve</creatorcontrib><creatorcontrib>O'Neill, Kim</creatorcontrib><creatorcontrib>Del Vecchio, Robert A.</creatorcontrib><creatorcontrib>McBriar, Mark</creatorcontrib><creatorcontrib>Guzik, Henry</creatorcontrib><creatorcontrib>Clader, John</creatorcontrib><creatorcontrib>Hawes, Brian E.</creatorcontrib><creatorcontrib>Hwa, Joyce</creatorcontrib><title>Effects of a selective melanin-concentrating hormone 1 receptor antagonist on food intake and energy homeostasis in diet-induced obese mice</title><title>European journal of pharmacology</title><addtitle>Eur J Pharmacol</addtitle><description>Melanin concentrating hormone (MCH) is a cyclic neuropeptide expressed in the lateral hypothalamus that plays an important role in energy homeostasis. To investigate the pharmacological consequences of inhibiting MCH signaling in murine obesity models, we examined the effect of acute and chronic administration of a selective MCH1 receptor antagonist (SCH-A) in diet-induced obese (DIO) and
Lep
ob/ob
mice. Oral administration of SCH-A for 5 consecutive days (30 mg/kg q.d.) produced hypophagia, a loss of body weight and adiposity, and decreased plasma leptin levels in DIO mice, and hypophagia and reduced weight gain in
Lep
ob/ob
mice. Chronic administration of SCH-A to DIO mice decreased food intake, body weight and adiposity, and plasma leptin and free fatty acids. These effects were accompanied by increases in several hypothalamic neuropeptides. Acute administration of SCH-A (30 mg/kg) prevented the decrease in energy expenditure associated with food restriction. These results indicate that MCH1 receptor antagonists may be effective in the treatment of obesity.</description><subject>Adipose Tissue - drug effects</subject><subject>Administration, Oral</subject><subject>Animals</subject><subject>Binding, Competitive</subject><subject>Biological and medical sciences</subject><subject>Body Weight - drug effects</subject><subject>Brain - metabolism</subject><subject>CHO Cells</subject><subject>Cricetinae</subject><subject>Cricetulus</subject><subject>Dietary Fats - administration & dosage</subject><subject>Dose-Response Relationship, Drug</subject><subject>Eating - drug effects</subject><subject>Energy Metabolism - drug effects</subject><subject>Fatty Acids, Nonesterified - blood</subject><subject>Female</subject><subject>Galanin - genetics</subject><subject>Gene Expression - drug effects</subject><subject>Homeostasis - drug effects</subject><subject>Hypothalamic Hormones - genetics</subject><subject>Hypothalamus - drug effects</subject><subject>Hypothalamus - metabolism</subject><subject>Indirect calorimetry</subject><subject>Insulin - blood</subject><subject>Intracellular Signaling Peptides and Proteins - genetics</subject><subject>Iodine Radioisotopes</subject><subject>Leptin - blood</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Melanin-concentrating hormone</subject><subject>Melanins - genetics</subject><subject>Metabolic diseases</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Obese</subject><subject>Neuropeptide Y - genetics</subject><subject>Neuropeptides - genetics</subject><subject>Nitriles - administration & dosage</subject><subject>Nitriles - pharmacology</subject><subject>Obesity</subject><subject>Obesity - etiology</subject><subject>Obesity - physiopathology</subject><subject>Oligopeptides - metabolism</subject><subject>Orexin Receptors</subject><subject>Orexins</subject><subject>Pharmacology. Drug treatments</subject><subject>Piperazines - administration & dosage</subject><subject>Piperazines - pharmacology</subject><subject>Pituitary Hormones - genetics</subject><subject>Protein Binding</subject><subject>Receptor antagonist</subject><subject>Receptors, G-Protein-Coupled</subject><subject>Receptors, Neuropeptide</subject><subject>Receptors, Somatostatin - antagonists & inhibitors</subject><subject>Receptors, Somatostatin - genetics</subject><subject>Receptors, Somatostatin - metabolism</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Triglycerides - blood</subject><subject>Urea - administration & dosage</subject><subject>Urea - analogs & derivatives</subject><subject>Urea - pharmacology</subject><issn>0014-2999</issn><issn>1879-0712</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc9uEzEQh1cIREPhDRDyBW67zOwf23tBQlWhSJW4wNly7HHqkLWD7VTqM_DSdZRIvdGTZc8387P9Nc17hA4B-edtR9v9nU5dD8A7wA54_6JZoRRzCwL7l80KAMe2n-f5onmT8xYAprmfXjcXyKcREMZV8-_aOTIls-iYZpl2dePviS2008GH1sRgKJSkiw8bdhfTEgMxZIkM7UtMTIeiNzH4XFgMzMVoma9Hf6hWLKNAafNQ-xaKuejsc60y66m0PtiDIcvimnLN84beNq-c3mV6d14vm9_frn9d3bS3P7__uPp625qxx9Li4ECiHECPyB3JQaLAaT2JtRyslVKIYXBrMZpxmLRzEtDxgSQ6MQnunB0um0-nufsU_x4oF7X4bGhXX0zxkBUXEseJT8-Cx1wuRqjgeAJNijkncmqf_KLTg0JQR1tqq0621NGWAlTVVm37cJ5_WC9kn5rOeirw8QzobPTOJR2Mz0-c4APAfMz_cuKoftu9p6Sy8VTNWV9FFWWj__9NHgEr8rYd</recordid><startdate>20060327</startdate><enddate>20060327</enddate><creator>Kowalski, Timothy J.</creator><creator>Spar, Brian D.</creator><creator>Weig, Blair</creator><creator>Farley, Constance</creator><creator>Cook, John</creator><creator>Ghibaudi, Lorraine</creator><creator>Fried, Steve</creator><creator>O'Neill, Kim</creator><creator>Del Vecchio, Robert A.</creator><creator>McBriar, Mark</creator><creator>Guzik, Henry</creator><creator>Clader, John</creator><creator>Hawes, Brian E.</creator><creator>Hwa, Joyce</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7X8</scope></search><sort><creationdate>20060327</creationdate><title>Effects of a selective melanin-concentrating hormone 1 receptor antagonist on food intake and energy homeostasis in diet-induced obese mice</title><author>Kowalski, Timothy J. ; Spar, Brian D. ; Weig, Blair ; Farley, Constance ; Cook, John ; Ghibaudi, Lorraine ; Fried, Steve ; O'Neill, Kim ; Del Vecchio, Robert A. ; McBriar, Mark ; Guzik, Henry ; Clader, John ; Hawes, Brian E. ; Hwa, Joyce</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c421t-13f081830a416fe8381715b57b83dd887733fb74c435aff801f63e81f7576ffd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Adipose Tissue - drug effects</topic><topic>Administration, Oral</topic><topic>Animals</topic><topic>Binding, Competitive</topic><topic>Biological and medical sciences</topic><topic>Body Weight - drug effects</topic><topic>Brain - metabolism</topic><topic>CHO Cells</topic><topic>Cricetinae</topic><topic>Cricetulus</topic><topic>Dietary Fats - administration & dosage</topic><topic>Dose-Response Relationship, Drug</topic><topic>Eating - drug effects</topic><topic>Energy Metabolism - drug effects</topic><topic>Fatty Acids, Nonesterified - blood</topic><topic>Female</topic><topic>Galanin - genetics</topic><topic>Gene Expression - drug effects</topic><topic>Homeostasis - drug effects</topic><topic>Hypothalamic Hormones - genetics</topic><topic>Hypothalamus - drug effects</topic><topic>Hypothalamus - metabolism</topic><topic>Indirect calorimetry</topic><topic>Insulin - blood</topic><topic>Intracellular Signaling Peptides and Proteins - genetics</topic><topic>Iodine Radioisotopes</topic><topic>Leptin - blood</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Melanin-concentrating hormone</topic><topic>Melanins - genetics</topic><topic>Metabolic diseases</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Obese</topic><topic>Neuropeptide Y - genetics</topic><topic>Neuropeptides - genetics</topic><topic>Nitriles - administration & dosage</topic><topic>Nitriles - pharmacology</topic><topic>Obesity</topic><topic>Obesity - etiology</topic><topic>Obesity - physiopathology</topic><topic>Oligopeptides - metabolism</topic><topic>Orexin Receptors</topic><topic>Orexins</topic><topic>Pharmacology. Drug treatments</topic><topic>Piperazines - administration & dosage</topic><topic>Piperazines - pharmacology</topic><topic>Pituitary Hormones - genetics</topic><topic>Protein Binding</topic><topic>Receptor antagonist</topic><topic>Receptors, G-Protein-Coupled</topic><topic>Receptors, Neuropeptide</topic><topic>Receptors, Somatostatin - antagonists & inhibitors</topic><topic>Receptors, Somatostatin - genetics</topic><topic>Receptors, Somatostatin - metabolism</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Triglycerides - blood</topic><topic>Urea - administration & dosage</topic><topic>Urea - analogs & derivatives</topic><topic>Urea - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kowalski, Timothy J.</creatorcontrib><creatorcontrib>Spar, Brian D.</creatorcontrib><creatorcontrib>Weig, Blair</creatorcontrib><creatorcontrib>Farley, Constance</creatorcontrib><creatorcontrib>Cook, John</creatorcontrib><creatorcontrib>Ghibaudi, Lorraine</creatorcontrib><creatorcontrib>Fried, Steve</creatorcontrib><creatorcontrib>O'Neill, Kim</creatorcontrib><creatorcontrib>Del Vecchio, Robert A.</creatorcontrib><creatorcontrib>McBriar, Mark</creatorcontrib><creatorcontrib>Guzik, Henry</creatorcontrib><creatorcontrib>Clader, John</creatorcontrib><creatorcontrib>Hawes, Brian E.</creatorcontrib><creatorcontrib>Hwa, Joyce</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kowalski, Timothy J.</au><au>Spar, Brian D.</au><au>Weig, Blair</au><au>Farley, Constance</au><au>Cook, John</au><au>Ghibaudi, Lorraine</au><au>Fried, Steve</au><au>O'Neill, Kim</au><au>Del Vecchio, Robert A.</au><au>McBriar, Mark</au><au>Guzik, Henry</au><au>Clader, John</au><au>Hawes, Brian E.</au><au>Hwa, Joyce</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of a selective melanin-concentrating hormone 1 receptor antagonist on food intake and energy homeostasis in diet-induced obese mice</atitle><jtitle>European journal of pharmacology</jtitle><addtitle>Eur J Pharmacol</addtitle><date>2006-03-27</date><risdate>2006</risdate><volume>535</volume><issue>1</issue><spage>182</spage><epage>191</epage><pages>182-191</pages><issn>0014-2999</issn><eissn>1879-0712</eissn><coden>EJPHAZ</coden><abstract>Melanin concentrating hormone (MCH) is a cyclic neuropeptide expressed in the lateral hypothalamus that plays an important role in energy homeostasis. To investigate the pharmacological consequences of inhibiting MCH signaling in murine obesity models, we examined the effect of acute and chronic administration of a selective MCH1 receptor antagonist (SCH-A) in diet-induced obese (DIO) and
Lep
ob/ob
mice. Oral administration of SCH-A for 5 consecutive days (30 mg/kg q.d.) produced hypophagia, a loss of body weight and adiposity, and decreased plasma leptin levels in DIO mice, and hypophagia and reduced weight gain in
Lep
ob/ob
mice. Chronic administration of SCH-A to DIO mice decreased food intake, body weight and adiposity, and plasma leptin and free fatty acids. These effects were accompanied by increases in several hypothalamic neuropeptides. Acute administration of SCH-A (30 mg/kg) prevented the decrease in energy expenditure associated with food restriction. These results indicate that MCH1 receptor antagonists may be effective in the treatment of obesity.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>16540104</pmid><doi>10.1016/j.ejphar.2006.01.062</doi><tpages>10</tpages></addata></record> |
| fulltext | fulltext |
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| ispartof | European journal of pharmacology, 2006-03, Vol.535 (1), p.182-191 |
| issn | 0014-2999 1879-0712 |
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| subjects | Adipose Tissue - drug effects Administration, Oral Animals Binding, Competitive Biological and medical sciences Body Weight - drug effects Brain - metabolism CHO Cells Cricetinae Cricetulus Dietary Fats - administration & dosage Dose-Response Relationship, Drug Eating - drug effects Energy Metabolism - drug effects Fatty Acids, Nonesterified - blood Female Galanin - genetics Gene Expression - drug effects Homeostasis - drug effects Hypothalamic Hormones - genetics Hypothalamus - drug effects Hypothalamus - metabolism Indirect calorimetry Insulin - blood Intracellular Signaling Peptides and Proteins - genetics Iodine Radioisotopes Leptin - blood Male Medical sciences Melanin-concentrating hormone Melanins - genetics Metabolic diseases Mice Mice, Inbred C57BL Mice, Obese Neuropeptide Y - genetics Neuropeptides - genetics Nitriles - administration & dosage Nitriles - pharmacology Obesity Obesity - etiology Obesity - physiopathology Oligopeptides - metabolism Orexin Receptors Orexins Pharmacology. Drug treatments Piperazines - administration & dosage Piperazines - pharmacology Pituitary Hormones - genetics Protein Binding Receptor antagonist Receptors, G-Protein-Coupled Receptors, Neuropeptide Receptors, Somatostatin - antagonists & inhibitors Receptors, Somatostatin - genetics Receptors, Somatostatin - metabolism Reverse Transcriptase Polymerase Chain Reaction Triglycerides - blood Urea - administration & dosage Urea - analogs & derivatives Urea - pharmacology |
| title | Effects of a selective melanin-concentrating hormone 1 receptor antagonist on food intake and energy homeostasis in diet-induced obese mice |
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