Ghrelin Treatment of Chronic Kidney Disease: Improvements in Lean Body Mass and Cytokine Profile
Chronic kidney disease (CKD) is associated with an increase in inflammatory cytokines and can result in cachexia with loss of muscle and fat stores. We previously demonstrated the efficacy of treating a model of cancer cachexia with ghrelin and a ghrelin receptor agonist. Currently, we examine a sur...
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| Veröffentlicht in: | Endocrinology (Philadelphia) 2008-02, Vol.149 (2), p.827-835 |
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| creator | DeBoer, Mark D Zhu, Xinxia Levasseur, Peter R Inui, Akio Hu, Zhaoyong Han, Guofeng Mitch, William E Taylor, John E Halem, Heather A Dong, Jesse Z Datta, Rakesh Culler, Michael D Marks, Daniel L |
| description | Chronic kidney disease (CKD) is associated with an increase in inflammatory cytokines and can result in cachexia with loss of muscle and fat stores. We previously demonstrated the efficacy of treating a model of cancer cachexia with ghrelin and a ghrelin receptor agonist. Currently, we examine a surgical model of CKD in rats, resulting in uremia and decreased accrual of lean body mass. Treatment with ghrelin and two ghrelin receptor agonists (BIM-28125 and BIM-28131) resulted in increased food intake and an improvement in lean body mass accrual that was related in part to a decrease in muscle protein degradation as assessed by muscle levels of the 14-kDa actin fragment resulting from cleaved actomyosin. Additionally, there was a decrease in circulating inflammatory cytokines in nephrectomized animals treated with ghrelin relative to saline treatment. Ghrelin-treated animals also had a decrease in the expression of IL-1 receptor in the brainstem and a decrease in expression of prohormone convertase-2, an enzyme involved in the processing of proopiomelanocortin to the anorexigenic peptide α-MSH. We conclude that ghrelin treatment in uremia results in improved lean mass accrual in part due to suppressed muscle proteolysis and possibly related to antiinflammatory effects. |
| doi_str_mv | 10.1210/en.2007-1046 |
| format | Article |
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We previously demonstrated the efficacy of treating a model of cancer cachexia with ghrelin and a ghrelin receptor agonist. Currently, we examine a surgical model of CKD in rats, resulting in uremia and decreased accrual of lean body mass. Treatment with ghrelin and two ghrelin receptor agonists (BIM-28125 and BIM-28131) resulted in increased food intake and an improvement in lean body mass accrual that was related in part to a decrease in muscle protein degradation as assessed by muscle levels of the 14-kDa actin fragment resulting from cleaved actomyosin. Additionally, there was a decrease in circulating inflammatory cytokines in nephrectomized animals treated with ghrelin relative to saline treatment. Ghrelin-treated animals also had a decrease in the expression of IL-1 receptor in the brainstem and a decrease in expression of prohormone convertase-2, an enzyme involved in the processing of proopiomelanocortin to the anorexigenic peptide α-MSH. We conclude that ghrelin treatment in uremia results in improved lean mass accrual in part due to suppressed muscle proteolysis and possibly related to antiinflammatory effects.</description><identifier>ISSN: 0013-7227</identifier><identifier>EISSN: 1945-7170</identifier><identifier>DOI: 10.1210/en.2007-1046</identifier><identifier>PMID: 18039782</identifier><identifier>CODEN: ENDOAO</identifier><language>eng</language><publisher>Bethesda, MD: Endocrine Society</publisher><subject>Absorptiometry, Photon ; Actin ; Actomyosin ; Agonists ; Animals ; Biodegradation ; Biological and medical sciences ; Body mass ; Body Weight - drug effects ; Brain stem ; Cachexia ; Cachexia - drug therapy ; Cachexia - etiology ; Cachexia - immunology ; Cytokines ; Cytokines - blood ; Cytokines - genetics ; Dactinomycin - metabolism ; Disease Models, Animal ; Eating - drug effects ; Food intake ; Fundamental and applied biological sciences. Psychology ; Gene Expression - drug effects ; Ghrelin ; Ghrelin - pharmacology ; Growth Hormone - blood ; Inflammation - blood ; Inflammation - drug therapy ; Inflammation - etiology ; Insulin-Like Growth Factor I - metabolism ; Interleukin 1 receptors ; Kidney diseases ; Kidneys ; Lean body mass ; Male ; Medical sciences ; Muscle, Skeletal - drug effects ; Muscle, Skeletal - metabolism ; Muscles ; Nephrectomy ; Nephrology. Urinary tract diseases ; Nephropathies. Renovascular diseases. Renal failure ; Neuropeptides - genetics ; Proopiomelanocortin ; Proprotein convertases ; Proteolysis ; Rats ; Rats, Inbred F344 ; Receptors ; Receptors, Ghrelin - agonists ; Renal failure ; Renal Insufficiency, Chronic - complications ; Renal Insufficiency, Chronic - drug therapy ; Renal Insufficiency, Chronic - immunology ; RNA, Messenger - metabolism ; Uremia ; Urinary system involvement in other diseases. Miscellaneous ; Vertebrates: endocrinology</subject><ispartof>Endocrinology (Philadelphia), 2008-02, Vol.149 (2), p.827-835</ispartof><rights>Copyright © 2008 by the Endocrine Society 2008</rights><rights>2008 INIST-CNRS</rights><rights>Copyright © 2008 by the Endocrine Society</rights><rights>Copyright © 2008 by The Endocrine Society 2008</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c582t-82ebb924ed8832aaa2129a3c700ef495a03eee3dc8cd9162b2d37b81b4a50ca93</citedby><cites>FETCH-LOGICAL-c582t-82ebb924ed8832aaa2129a3c700ef495a03eee3dc8cd9162b2d37b81b4a50ca93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20031486$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18039782$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>DeBoer, Mark D</creatorcontrib><creatorcontrib>Zhu, Xinxia</creatorcontrib><creatorcontrib>Levasseur, Peter R</creatorcontrib><creatorcontrib>Inui, Akio</creatorcontrib><creatorcontrib>Hu, Zhaoyong</creatorcontrib><creatorcontrib>Han, Guofeng</creatorcontrib><creatorcontrib>Mitch, William E</creatorcontrib><creatorcontrib>Taylor, John E</creatorcontrib><creatorcontrib>Halem, Heather A</creatorcontrib><creatorcontrib>Dong, Jesse Z</creatorcontrib><creatorcontrib>Datta, Rakesh</creatorcontrib><creatorcontrib>Culler, Michael D</creatorcontrib><creatorcontrib>Marks, Daniel L</creatorcontrib><title>Ghrelin Treatment of Chronic Kidney Disease: Improvements in Lean Body Mass and Cytokine Profile</title><title>Endocrinology (Philadelphia)</title><addtitle>Endocrinology</addtitle><description>Chronic kidney disease (CKD) is associated with an increase in inflammatory cytokines and can result in cachexia with loss of muscle and fat stores. We previously demonstrated the efficacy of treating a model of cancer cachexia with ghrelin and a ghrelin receptor agonist. Currently, we examine a surgical model of CKD in rats, resulting in uremia and decreased accrual of lean body mass. Treatment with ghrelin and two ghrelin receptor agonists (BIM-28125 and BIM-28131) resulted in increased food intake and an improvement in lean body mass accrual that was related in part to a decrease in muscle protein degradation as assessed by muscle levels of the 14-kDa actin fragment resulting from cleaved actomyosin. Additionally, there was a decrease in circulating inflammatory cytokines in nephrectomized animals treated with ghrelin relative to saline treatment. Ghrelin-treated animals also had a decrease in the expression of IL-1 receptor in the brainstem and a decrease in expression of prohormone convertase-2, an enzyme involved in the processing of proopiomelanocortin to the anorexigenic peptide α-MSH. We conclude that ghrelin treatment in uremia results in improved lean mass accrual in part due to suppressed muscle proteolysis and possibly related to antiinflammatory effects.</description><subject>Absorptiometry, Photon</subject><subject>Actin</subject><subject>Actomyosin</subject><subject>Agonists</subject><subject>Animals</subject><subject>Biodegradation</subject><subject>Biological and medical sciences</subject><subject>Body mass</subject><subject>Body Weight - drug effects</subject><subject>Brain stem</subject><subject>Cachexia</subject><subject>Cachexia - drug therapy</subject><subject>Cachexia - etiology</subject><subject>Cachexia - immunology</subject><subject>Cytokines</subject><subject>Cytokines - blood</subject><subject>Cytokines - genetics</subject><subject>Dactinomycin - metabolism</subject><subject>Disease Models, Animal</subject><subject>Eating - drug effects</subject><subject>Food intake</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression - drug effects</subject><subject>Ghrelin</subject><subject>Ghrelin - pharmacology</subject><subject>Growth Hormone - blood</subject><subject>Inflammation - blood</subject><subject>Inflammation - drug therapy</subject><subject>Inflammation - etiology</subject><subject>Insulin-Like Growth Factor I - metabolism</subject><subject>Interleukin 1 receptors</subject><subject>Kidney diseases</subject><subject>Kidneys</subject><subject>Lean body mass</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Muscle, Skeletal - drug effects</subject><subject>Muscle, Skeletal - metabolism</subject><subject>Muscles</subject><subject>Nephrectomy</subject><subject>Nephrology. Urinary tract diseases</subject><subject>Nephropathies. Renovascular diseases. Renal failure</subject><subject>Neuropeptides - genetics</subject><subject>Proopiomelanocortin</subject><subject>Proprotein convertases</subject><subject>Proteolysis</subject><subject>Rats</subject><subject>Rats, Inbred F344</subject><subject>Receptors</subject><subject>Receptors, Ghrelin - agonists</subject><subject>Renal failure</subject><subject>Renal Insufficiency, Chronic - complications</subject><subject>Renal Insufficiency, Chronic - drug therapy</subject><subject>Renal Insufficiency, Chronic - immunology</subject><subject>RNA, Messenger - metabolism</subject><subject>Uremia</subject><subject>Urinary system involvement in other diseases. Miscellaneous</subject><subject>Vertebrates: endocrinology</subject><issn>0013-7227</issn><issn>1945-7170</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kc1v1DAQxS1ERZfCjTOyhCoupPgrG4cDEixQKhbBoZzNxJmwLlk7tbOV9r_H0UYtleA0subn997oEfKMszMuOHuN_kwwVhWcqeUDsuC1KouKV-whWTDGZVEJUR2Txyld5adSSj4ix1wzWVdaLMjP803E3nl6GRHGLfqRho6uNjF4Z-kX13rc0w8uISR8Qy-2Qww3OGGJ5k9rBE_fh3ZPv0JKFHxLV_sx_HYe6fcYOtfjE3LUQZ_w6TxPyI9PHy9Xn4v1t_OL1bt1YUstxkILbJpaKGy1lgIABBc1SFsxhp2qS2ASEWVrtW1rvhSNaGXVaN4oKJmFWp6QtwfdYddssbU5YoTeDNFtIe5NAGfub7zbmF_hxgjBa8lVFngxC8RwvcM0mquwiz5nNpJLVmpVLXWmXh0oG0NKEbtbB87M1IdBb6Y-zNRHxp__neoOngvIwOkMQLLQdxG8demWy0o5m56EXh64sBv-Z1nMlvJAom-DjbmKIWJKd9f8M-gftJuwrA</recordid><startdate>20080201</startdate><enddate>20080201</enddate><creator>DeBoer, Mark D</creator><creator>Zhu, Xinxia</creator><creator>Levasseur, Peter R</creator><creator>Inui, Akio</creator><creator>Hu, Zhaoyong</creator><creator>Han, Guofeng</creator><creator>Mitch, William E</creator><creator>Taylor, John E</creator><creator>Halem, Heather A</creator><creator>Dong, Jesse Z</creator><creator>Datta, Rakesh</creator><creator>Culler, Michael D</creator><creator>Marks, Daniel L</creator><general>Endocrine Society</general><general>Oxford University Press</general><general>The Endocrine Society</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>7QG</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>5PM</scope></search><sort><creationdate>20080201</creationdate><title>Ghrelin Treatment of Chronic Kidney Disease: Improvements in Lean Body Mass and Cytokine Profile</title><author>DeBoer, Mark D ; Zhu, Xinxia ; Levasseur, Peter R ; Inui, Akio ; Hu, Zhaoyong ; Han, Guofeng ; Mitch, William E ; Taylor, John E ; Halem, Heather A ; Dong, Jesse Z ; Datta, Rakesh ; Culler, Michael D ; Marks, Daniel L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c582t-82ebb924ed8832aaa2129a3c700ef495a03eee3dc8cd9162b2d37b81b4a50ca93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Absorptiometry, Photon</topic><topic>Actin</topic><topic>Actomyosin</topic><topic>Agonists</topic><topic>Animals</topic><topic>Biodegradation</topic><topic>Biological and medical sciences</topic><topic>Body mass</topic><topic>Body Weight - drug effects</topic><topic>Brain stem</topic><topic>Cachexia</topic><topic>Cachexia - drug therapy</topic><topic>Cachexia - etiology</topic><topic>Cachexia - immunology</topic><topic>Cytokines</topic><topic>Cytokines - blood</topic><topic>Cytokines - genetics</topic><topic>Dactinomycin - metabolism</topic><topic>Disease Models, Animal</topic><topic>Eating - drug effects</topic><topic>Food intake</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression - drug effects</topic><topic>Ghrelin</topic><topic>Ghrelin - pharmacology</topic><topic>Growth Hormone - blood</topic><topic>Inflammation - blood</topic><topic>Inflammation - drug therapy</topic><topic>Inflammation - etiology</topic><topic>Insulin-Like Growth Factor I - metabolism</topic><topic>Interleukin 1 receptors</topic><topic>Kidney diseases</topic><topic>Kidneys</topic><topic>Lean body mass</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Muscle, Skeletal - drug effects</topic><topic>Muscle, Skeletal - metabolism</topic><topic>Muscles</topic><topic>Nephrectomy</topic><topic>Nephrology. Urinary tract diseases</topic><topic>Nephropathies. Renovascular diseases. Renal failure</topic><topic>Neuropeptides - genetics</topic><topic>Proopiomelanocortin</topic><topic>Proprotein convertases</topic><topic>Proteolysis</topic><topic>Rats</topic><topic>Rats, Inbred F344</topic><topic>Receptors</topic><topic>Receptors, Ghrelin - agonists</topic><topic>Renal failure</topic><topic>Renal Insufficiency, Chronic - complications</topic><topic>Renal Insufficiency, Chronic - drug therapy</topic><topic>Renal Insufficiency, Chronic - immunology</topic><topic>RNA, Messenger - metabolism</topic><topic>Uremia</topic><topic>Urinary system involvement in other diseases. 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We previously demonstrated the efficacy of treating a model of cancer cachexia with ghrelin and a ghrelin receptor agonist. Currently, we examine a surgical model of CKD in rats, resulting in uremia and decreased accrual of lean body mass. Treatment with ghrelin and two ghrelin receptor agonists (BIM-28125 and BIM-28131) resulted in increased food intake and an improvement in lean body mass accrual that was related in part to a decrease in muscle protein degradation as assessed by muscle levels of the 14-kDa actin fragment resulting from cleaved actomyosin. Additionally, there was a decrease in circulating inflammatory cytokines in nephrectomized animals treated with ghrelin relative to saline treatment. Ghrelin-treated animals also had a decrease in the expression of IL-1 receptor in the brainstem and a decrease in expression of prohormone convertase-2, an enzyme involved in the processing of proopiomelanocortin to the anorexigenic peptide α-MSH. We conclude that ghrelin treatment in uremia results in improved lean mass accrual in part due to suppressed muscle proteolysis and possibly related to antiinflammatory effects.</abstract><cop>Bethesda, MD</cop><pub>Endocrine Society</pub><pmid>18039782</pmid><doi>10.1210/en.2007-1046</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Oxford University Press; Alma/SFX Local Collection; EZB Electronic Journals Library |
| subjects | Absorptiometry, Photon Actin Actomyosin Agonists Animals Biodegradation Biological and medical sciences Body mass Body Weight - drug effects Brain stem Cachexia Cachexia - drug therapy Cachexia - etiology Cachexia - immunology Cytokines Cytokines - blood Cytokines - genetics Dactinomycin - metabolism Disease Models, Animal Eating - drug effects Food intake Fundamental and applied biological sciences. Psychology Gene Expression - drug effects Ghrelin Ghrelin - pharmacology Growth Hormone - blood Inflammation - blood Inflammation - drug therapy Inflammation - etiology Insulin-Like Growth Factor I - metabolism Interleukin 1 receptors Kidney diseases Kidneys Lean body mass Male Medical sciences Muscle, Skeletal - drug effects Muscle, Skeletal - metabolism Muscles Nephrectomy Nephrology. Urinary tract diseases Nephropathies. Renovascular diseases. Renal failure Neuropeptides - genetics Proopiomelanocortin Proprotein convertases Proteolysis Rats Rats, Inbred F344 Receptors Receptors, Ghrelin - agonists Renal failure Renal Insufficiency, Chronic - complications Renal Insufficiency, Chronic - drug therapy Renal Insufficiency, Chronic - immunology RNA, Messenger - metabolism Uremia Urinary system involvement in other diseases. Miscellaneous Vertebrates: endocrinology |
| title | Ghrelin Treatment of Chronic Kidney Disease: Improvements in Lean Body Mass and Cytokine Profile |
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