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 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 alpha-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.
Department of Pediatrics, University of Virginia, Charlottesville, VA 22908, USA.
Mark D
MD
Deboer
Xinxia
X
Zhu
Peter R
PR
Levasseur
Akio
A
Inui
Zhaoyong
Z
Hu
Guofeng
G
Han
William E
WE
Mitch
John E
JE
Taylor
Heather A
HA
Halem
Jesse Z
JZ
Dong
Rakesh
R
Datta
Michael D
MD
Culler
Daniel L
DL
Marks
D015502:Absorptiometry, Photon; D000818:Animals; D001835:Body Weight / Q000187:drug effects*; D002100:Cachexia / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology; D016207:Cytokines / Q000097:blood* / Q000235:genetics; D003609:Dactinomycin / Q000378:metabolism; D004195:Disease Models, Animal; D004435:Eating / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D054439:Ghrelin / Q000494:pharmacology*; D013006:Growth Hormone / Q000097:blood; D007249:Inflammation / Q000097:blood / Q000188:drug therapy / Q000209:etiology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009392:Nephrectomy; D009479:Neuropeptides / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D054440:Receptors, Ghrelin / Q000819:agonists; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000188:drug therapy* / Q000276:immunology
D016207:Cytokines; D054439:Ghrelin; D009479:Neuropeptides; D012333:RNA, Messenger; D054440:Receptors, Ghrelin; D003609:Dactinomycin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone