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- Title
The GOAT-Ghrelin System Is Not Essential for Hypoglycemia Prevention during Prolonged Calorie Restriction.
- Authors
Chun-Xia Yi; Heppner, Kristy M.; Kirchner, Henriette; Jenny Tong; Bielohuby, Maximillian; Gaylinn, Bruce D.; Müller, Timo D.; Bartley, Erin; Davis, Harold W.; Yongmei Zhao; Joseph, Anupama; Kruthaupt, Traci; Ottaway, Nickki; Kabra, Dhiraj; Habegger, Kirk M.; Benoit, Stephen C.; Bidlingmaier, Martin; Thorner, Michael O.; Perez-Tilve, Diego; Tschöp, Matthias H.
- Abstract
Objective: Ghrelin acylation by ghrelin O-acyltransferase (GOAT) has recently been reported to be essential for the prevention of hypoglycemia during prolonged negative energy balance. Using a unique set of four different genetic loss-offunction models for the GOAT/ghrelin/growth hormone secretagogue receptor (GHSR) system, we thoroughly tested the hypothesis that lack-of-ghrelin activation or signaling would lead to hypoglycemia during caloric deprivation. Methodology: Male and female knockout (KO) mice for GOAT, ghrelin, GHSR, or both ghrelin and GHSR (dKO) were subjected to prolonged calorie restriction (40% of ad libitum chow intake). Body weight, fat mass, and glucose levels were recorded daily and compared to wildtype (WT) controls. Forty-eight hour blood glucose profiles were generated for each individual mouse when 2% or less body fat mass was reached. Blood samples were obtained for analysis of circulating levels of acyl- and desacyl-ghrelin, IGF-1, and insulin. Principal Findings: Chronic calorie restriction progressively decreased body weight and body fat mass in all mice regardless of genotype. When fat mass was depleted to 2% or less of body weight for 2 consecutive days, random hypoglycemic events occurred in some mice across all genotypes. There was no increase in the incidence of hypoglycemia in any of the four loss-of-function models for ghrelin signaling including GOAT KO mice. Furthermore, no differences in insulin or IGF-1 levels were observed between genotypes. Conclusion: The endogenous GOAT-ghrelin-GHSR system is not essential for the maintenance of euglycemia during prolonged calorie restriction.
- Subjects
HYPOGLYCEMIA; GHRELIN; LOW-calorie diet; ACYLATION; HORMONES; BLOOD sugar
- Publication
PLoS ONE, 2012, Vol 7, Issue 2, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0032100