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

Content Provider	PubMed Central
Author	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.
Abstract	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.
Related Links	http://dx.doi.org/10.1073/pnas.1002271107
Starting Page	7467
File Format	PDF
ISSN	10916490
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	16
Volume Number	107
Language	English
Publisher	National Academy of Sciences
Publisher Date	2010-04-20
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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