Submitted on July 18, 2007
Accepted on January 14, 2008
Mice with chronically increased circulating ghrelin develop age-related glucose intolerance
Jackie Reed, Stephen C Benoit1, Paul Thomas Pfluger2, Matthias Tschoep3, David D'Alessio, and Randy J Seeley4*
1 Psychiatry, University of Cincinnati, Cincinnati, Ohio, United States
2 Psychiatry, Obesity Research Center, Cincinnati, Ohio, United States
3 United States
4 Psychiatry, University of Cincinnati, Cincinnati, Ohio, United States; Psychiatry, University of Cincinnati, United States
* To whom correspondence should be addressed. E-mail: randy.seeley{at}uc.edu.
Ghrelin is a gut peptide that stimulates food intake and increases body fat mass when administered centrally or peripherally. In this study, ghrelin was overexpressed in neurons using the neuron-specific enolase (NSE) promoter sequences and mouse ghrelin cDNA (NSE-Ghr). Ghrelin expression in NSE-Ghr brain tissues was increased compared to wild-type mice. Ghrelin expression was also increased to a much smaller extent in liver of these mice, but mRNA levels in stomach or duodenum did not differ from wild-type mice. Body weight and composition was analyzed in two lines of NSE-Ghr mice, one line (L43) with increased circulating bioactive ghrelin, and one line (L73) without. No increases in body weight, food intake, or fat mass were found. Energy expenditure was measured in L43 mice, and did not differ from wild-type controls while locomotor activity was increased in NSE-Ghr mice Young NSE-Ghr mice had normal glucose tolerance, however, L43 NSE-Ghr mice, but not L73 mice, developed glucose intolerance at 32 weeks of age. Despite the impaired glucose tolerance in L43 mice, insulin levels did not differ from those of wild-type mice. These findings suggest a role for ghrelin in age-associated impairments of glucose homeostasis.
