Upregulation of ghrelin expression in cachectic nude mice bearing human melanoma cells.
Ghrelin is a gastrointestinal peptide that stimulates food intake and growth hormone (GH) secretion. We studied the biosynthesis and secretion of ghrelin in a cancer cachexia mouse model. G361, a human melanoma cell line, was inoculated into nude mice. The body weight was reduced and the plasma concentration of interleukin-1beta (IL-1beta) was markedly higher in tumor-inoculated mice compared with vehicle-treated mice. Furthermore, white adipose tissue (WAT) weight, blood sugar level, and plasma concentrations of leptin and nonesterified fatty acids (NEFA) were significantly lower in tumor-inoculated mice. The plasma concentration of ghrelin increased with the progression of cachexia. The levels of both ghrelin peptide and mRNA in the stomach were also upregulated in tumor-inoculated mice. This study demonstrates that both ghrelin biosynthesis and secretion are stimulated in the long-term negative energy balance of tumor-inoculated cachectic mice. These findings suggest the involvement of ghrelin in the regulation of energy homeostasis in cancer cachexia.
Hanada
Takeshi
T
Third Department of Internal Medicine, Miyazaki Medical College, Kiyotake, Japan.
Toshinai
Koji
K
Date
Yukari
Y
Kajimura
Naoko
N
Tsukada
Toshihiko
T
Hayashi
Yujiro
Y
Kangawa
Kenji
K
Nakazato
Masamitsu
M
D000273:Adipose Tissue / Q000473:pathology; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002100:Cachexia / Q000209:etiology / Q000378:metabolism*; D004734:Energy Metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D054439:Ghrelin; D006801:Humans; D007375:Interleukin-1 / Q000097:blood; D020738:Leptin / Q000097:blood; D008545:Melanoma / Q000150:complications*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009929:Organ Size; D036361:Peptide Hormones / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D013270:Stomach / Q000737:chemistry; D014407:Tumor Cells, Cultured; D015431:Weight Loss
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D054439:Ghrelin; D007375:Interleukin-1; D020738:Leptin; D036361:Peptide Hormones; D012333:RNA, Messenger