Glucose and weight control in mice with a designed ghrelin O-acyltransferase inhibitor.
Science
; 330(6011): 1689-92, 2010 Dec 17.
Article
in En
| MEDLINE
| ID: mdl-21097901
ABSTRACT
Ghrelin is a gastric peptide hormone that stimulates weight gain in vertebrates. The biological activities of ghrelin require octanoylation of the peptide on Ser(3), an unusual posttranslational modification that is catalyzed by the enzyme ghrelin O-acyltransferase (GOAT). Here, we describe the design, synthesis, and characterization of GO-CoA-Tat, a peptide-based bisubstrate analog that antagonizes GOAT. GO-CoA-Tat potently inhibits GOAT in vitro, in cultured cells, and in mice. Intraperitoneal administration of GO-CoA-Tat improves glucose tolerance and reduces weight gain in wild-type mice but not in ghrelin-deficient mice, supporting the concept that its beneficial metabolic effects are due specifically to GOAT inhibition. In addition to serving as a research tool for mapping ghrelin actions, GO-CoA-Tat may help pave the way for clinical targeting of GOAT in metabolic diseases.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Peptides
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Acyltransferases
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Weight Gain
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Enzyme Inhibitors
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Ghrelin
/
Glucose
Limits:
Animals
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Humans
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Male
Language:
En
Journal:
Science
Year:
2010
Document type:
Article
Affiliation country:
United States
Publication country:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
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EUA
/
UNITED STATES
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UNITED STATES OF AMERICA
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US
/
USA