Mice with chronically increased circulating ghrelin develop age-related glucose intolerance.
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 with 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 with increased circulating bioactive ghrelin (L43) and one line without (L73). 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, whereas 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 wk 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.
Reed
Jacquelyn A
JA
Department of Psychiatry, Genome Research Institute, University of Cincinnati, Cincinnati, OH 45237, USA.
Benoit
Stephen C
SC
Pfluger
Paul T
PT
Tschöp
Matthias H
MH
D'Alessio
David A
DA
Seeley
Randy J
RJ
D000273:Adipose Tissue / Q000502:physiology; D000375:Aging / Q000502:physiology*; D000818:Animals; D001823:Body Composition / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D004386:Duodenum / Q000502:physiology; D004435:Eating / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D054439:Ghrelin / Q000097:blood* / Q000235:genetics*; D018149:Glucose Intolerance / Q000378:metabolism* / Q000503:physiopathology*; D008099:Liver / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D013270:Stomach / Q000502:physiology
D054439:Ghrelin; D012333:RNA, Messenger