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Ghrelin O-acyltransferase (GOAT) is essential for growth hormone-mediated survival of calorie-restricted mice

Ghrelin O-acyltransferase (GOAT) attaches octanoate to proghrelin, which is processed to ghrelin, an octanoylated peptide hormone that stimulates release of growth hormone (GH) from pituitary cells. Elimination of the gene encoding ghrelin or its receptor produces only mild phenotypes in mice. Thus,... Full description

Journal Title: Proceedings of the National Academy of Sciences of the United States of America 2010, Vol.107(16), pp.7467-7472
Main Author: Zhao , Tong-Jin
Other Authors: Liang , Guosheng , Li , Robert Lin , Xie , Xuefen , Sleeman , Mark W. , Murphy , Andrew J. , Valenzuela , David M. , Yancopoulos , George D. , Goldstein , Joseph L. , Brown , Michael S.
Format: Electronic Article Electronic Article
Language: English
Subjects:
Publisher: National Academy of Sciences
Created: 2010
ID: ISSN: 0027-8424
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recordid: faoagrisUS201301831841
title: Ghrelin O-acyltransferase (GOAT) is essential for growth hormone-mediated survival of calorie-restricted mice
format: Article
creator:
  • Zhao , Tong-Jin
  • Liang , Guosheng
  • Li , Robert Lin
  • Xie , Xuefen
  • Sleeman , Mark W.
  • Murphy , Andrew J.
  • Valenzuela , David M.
  • Yancopoulos , George D.
  • Goldstein , Joseph L.
  • Brown , Michael S.
subjects:
  • Weight Loss
  • Blood Glucose
  • Octanoic Acid
  • Phenotype
  • Low Calorie Diet
  • Mutants
  • Mice
  • Ghrelin
  • Acyltransferases
  • Enzyme Activity
  • Mortality
  • Physical Activity
  • Body Weight
  • Somatotropin
  • Octanoylated Ghrelin
  • Ghrelin O-Acyltransferase
  • Proghrelin
ispartof: Proceedings of the National Academy of Sciences of the United States of America, 2010, Vol.107(16), pp.7467-7472
description: Ghrelin O-acyltransferase (GOAT) attaches octanoate to proghrelin, which is processed to ghrelin, an octanoylated peptide hormone that stimulates release of growth hormone (GH) from pituitary cells. Elimination of the gene encoding ghrelin or its receptor produces only mild phenotypes in mice. Thus, the essential function of ghrelin is obscure. Here, we eliminate the Goat gene in mice, thereby eliminating all octanoylated ghrelin from blood. On normal or high fat diets, Goat⁻/⁻ mice grew and maintained the same weights as wild-type (WT) littermates. When subjected to 60% calorie restriction, WT and Goat⁻/⁻ mice both lost 30% of body weight and 75% of body fat within 4 days. In both lines, fasting blood glucose initially declined equally. After 4 days, glucose stabilized in WT mice at 58-76 mg/dL. In Goat⁻/⁻ mice, glucose continued to decline, reaching 12-36 mg/dL on day 7. At this point, WT mice showed normal physical activity, whereas Goat⁻/⁻ mice were moribund. GH rose progressively in calorie-restricted WT mice and less in Goat⁻/⁻ mice. Infusion of either ghrelin or GH normalized blood glucose in Goat⁻/⁻ mice and prevented death. Thus, an essential function of ghrelin in mice is elevation of GH levels during severe calorie restriction, thereby preserving blood glucose and preventing death. ; Includes references ; p. 7467-7472.
language: eng
source:
identifier: ISSN: 0027-8424
fulltext: fulltext
issn:
  • 00278424
  • 0027-8424
url: Link


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titleGhrelin O-acyltransferase (GOAT) is essential for growth hormone-mediated survival of calorie-restricted mice
creatorZhao , Tong-Jin ; Liang , Guosheng ; Li , Robert Lin ; Xie , Xuefen ; Sleeman , Mark W. ; Murphy , Andrew J. ; Valenzuela , David M. ; Yancopoulos , George D. ; Goldstein , Joseph L. ; Brown , Michael S.
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ispartofProceedings of the National Academy of Sciences of the United States of America, 2010, Vol.107(16), pp.7467-7472
identifierISSN: 0027-8424
subjectWeight Loss ; Blood Glucose ; Octanoic Acid ; Phenotype ; Low Calorie Diet ; Mutants ; Mice ; Ghrelin ; Acyltransferases ; Enzyme Activity ; Mortality ; Physical Activity ; Body Weight ; Somatotropin ; Octanoylated Ghrelin ; Ghrelin O-Acyltransferase ; Proghrelin
descriptionGhrelin O-acyltransferase (GOAT) attaches octanoate to proghrelin, which is processed to ghrelin, an octanoylated peptide hormone that stimulates release of growth hormone (GH) from pituitary cells. Elimination of the gene encoding ghrelin or its receptor produces only mild phenotypes in mice. Thus, the essential function of ghrelin is obscure. Here, we eliminate the Goat gene in mice, thereby eliminating all octanoylated ghrelin from blood. On normal or high fat diets, Goat⁻/⁻ mice grew and maintained the same weights as wild-type (WT) littermates. When subjected to 60% calorie restriction, WT and Goat⁻/⁻ mice both lost 30% of body weight and 75% of body fat within 4 days. In both lines, fasting blood glucose initially declined equally. After 4 days, glucose stabilized in WT mice at 58-76 mg/dL. In Goat⁻/⁻ mice, glucose continued to decline, reaching 12-36 mg/dL on day 7. At this point, WT mice showed normal physical activity, whereas Goat⁻/⁻ mice were moribund. GH rose progressively in calorie-restricted WT mice and less in Goat⁻/⁻ mice. Infusion of either ghrelin or GH normalized blood glucose in Goat⁻/⁻ mice and prevented death. Thus, an essential function of ghrelin in mice is elevation of GH levels during severe calorie restriction, thereby preserving blood glucose and preventing death. ; Includes references ; p. 7467-7472.
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titleGhrelin O-acyltransferase (GOAT) is essential for growth hormone-mediated survival of calorie-restricted mice
descriptionGhrelin O-acyltransferase (GOAT) attaches octanoate to proghrelin, which is processed to ghrelin, an octanoylated peptide hormone that stimulates release of growth hormone (GH) from pituitary cells. Elimination of the gene encoding ghrelin or its receptor produces only mild phenotypes in mice. Thus, the essential function of ghrelin is obscure. Here, we eliminate the Goat gene in mice, thereby eliminating all octanoylated ghrelin from blood. On normal or high fat diets, Goat⁻/⁻ mice grew and maintained the same weights as wild-type (WT) littermates. When subjected to 60% calorie restriction, WT and Goat⁻/⁻ mice both lost 30% of body weight and 75% of body fat within 4 days. In both lines, fasting blood glucose initially declined equally. After 4 days, glucose stabilized in WT mice at 58-76 mg/dL. In Goat⁻/⁻ mice, glucose continued to decline, reaching 12-36 mg/dL on day 7. At this point, WT mice showed normal physical activity, whereas Goat⁻/⁻ mice were moribund. GH rose progressively in calorie-restricted WT mice and less in Goat⁻/⁻ mice. Infusion of either ghrelin or GH normalized blood glucose in Goat⁻/⁻ mice and prevented death. Thus, an essential function of ghrelin in mice is elevation of GH levels during severe calorie restriction, thereby preserving blood glucose and preventing death. ; Includes references ; p. 7467-7472.
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titleGhrelin O-acyltransferase (GOAT) is essential for growth hormone-mediated survival of calorie-restricted mice
authorZhao , Tong-Jin ; Liang , Guosheng ; Li , Robert Lin ; Xie , Xuefen ; Sleeman , Mark W. ; Murphy , Andrew J. ; Valenzuela , David M. ; Yancopoulos , George D. ; Goldstein , Joseph L. ; Brown , Michael S.
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8Acyltransferases
9Enzyme Activity
10Mortality
11Physical Activity
12Body Weight
13Somatotropin
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abstractGhrelin O-acyltransferase (GOAT) attaches octanoate to proghrelin, which is processed to ghrelin, an octanoylated peptide hormone that stimulates release of growth hormone (GH) from pituitary cells. Elimination of the gene encoding ghrelin or its receptor produces only mild phenotypes in mice. Thus, the essential function of ghrelin is obscure. Here, we eliminate the Goat gene in mice, thereby eliminating all octanoylated ghrelin from blood. On normal or high fat diets, Goat⁻/⁻ mice grew and maintained the same weights as wild-type (WT) littermates. When subjected to 60% calorie restriction, WT and Goat⁻/⁻ mice both lost 30% of body weight and 75% of body fat within 4 days. In both lines, fasting blood glucose initially declined equally. After 4 days, glucose stabilized in WT mice at 58-76 mg/dL. In Goat⁻/⁻ mice, glucose continued to decline, reaching 12-36 mg/dL on day 7. At this point, WT mice showed normal physical activity, whereas Goat⁻/⁻ mice were moribund. GH rose progressively in calorie-restricted WT mice and less in Goat⁻/⁻ mice. Infusion of either ghrelin or GH normalized blood glucose in Goat⁻/⁻ mice and prevented death. Thus, an essential function of ghrelin in mice is elevation of GH levels during severe calorie restriction, thereby preserving blood glucose and preventing death.
pubNational Academy of Sciences
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