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Am J Physiol Endocrinol Metab (September 20, 2005). doi:10.1152/ajpendo.00181.2005
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Submitted on April 27, 2005
Accepted on September 14, 2005

Growth Hormone Receptor Deficiency Results in Blunted Ghrelin Feeding Response, Obesity and Hypolipidemia in mice

Emil Egecioglu1*, Mikael Bjursell2, Anna Ljungberg3, Suzanne L Dickson1, John J Kopchick4, Goran Bergstrom1, Lennart Svensson5, Jan Oscarsson6, Jan Tornell2, and Mohammad Bohlooly-Y2

1 Department of Physiology, Gothenburg University, Gothenburg, Sweden
2 Department of Physiology, Gothenburg University, Gothenburg, Sweden; AstraZeneca R&D, Molndal, Sweden
3 Wallenberg lab, Gothenburg University, Gothenburg, Sweden
4 Department of Biomedical Sciences, Edison Biotechnology Institute, Ohio University, Athens, Ohio, USA
5 AstraZeneca R&D, Molndal, Sweden
6 Department of Physiology, Gothenburg University, Gothenburg, Sweden; AstraZeneca R&D, Molndal, Sweden; Wallenberg lab, Gothenburg University, Gothenburg, Sweden

* To whom correspondence should be addressed. E-mail: Emil.Egecioglu{at}medic.gu.se.

We have previously shown that growth hormone (GH) over-expression in the brain increased food intake, accompanied with increased hypothalamic agouti-related protein (AGRP) expression. Ghrelin, which stimulates both appetite and GH secretion, was injected intracerebroventricularly to GHR -/- and littermate control (+/+) mice to determine if ghrelins acute effects on appetite are dependent upon GHR signaling. GHR -/- mice were also analysed with respect to serum levels of lipoproteins, apolipoprotein (apo) B, leptin, glucose and insulin as well as body composition. Central injection of ghrelin into the third dorsal ventricle increased food consumption in +/+ mice whereas no change was observed in GHR -/- mice. After ghrelin injection, AGRP mRNA expression in the hypothalamus was higher in +/+ littermates than in GHR -/- mice, indicating a possible importance of AGRP in the GHR mediated effect of ghrelin. Compared to controls, GHR -/- mice had increased food intake, leptin levels and total and intra-abdominal fat mass per body weight, and deceased lean mass. Moreover, serum levels of triglycerides, LDL and HDL cholesterol, apo B as well as glucose and insulin levels were lower in the GHR -/- mice. In summary, ghrelins acute central action to increase food intake require functionally intact GHR-signaling. Long-term GH-deficiency in mice is associated with high plasma leptin levels, obesity and increased food intake but a marked decrease in all lipoprotein fractions.




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