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Diabetes 54:51-62, 2005
© 2005 by the American Diabetes Association, Inc.
Growth Hormone Overexpression in the Central Nervous System Results in Hyperphagia-Induced Obesity Associated With Insulin Resistance and Dyslipidemia
1 Department of Physiology, Göteborg University, Göteborg, Sweden
2 Department of Internal Medicine Research Centre for Endocrinology and Metabolism, Sahlgrenska University Hospital, Göteborg, Sweden
3 AstraZeneca Research and Development, Mölndal, Sweden
4 Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital, Göteborg, Sweden
5 AstraZeneca Research and Development, Alderley Park, Macclesfield, Cheshire, U.K
6 Department of Physiology Lund University, Lund, Sweden
7 Department of Medicine, Lund University, Lund, Sweden
It is well known that peripherally administered growth hormone (GH) results in decreased body fat mass. However, GH-deficient patients increase their food intake when substituted with GH, suggesting that GH also has an appetite stimulating effect. Transgenic mice with an overexpression of bovine GH in the central nervous system (CNS) were created to investigate the role of GH in CNS. This study shows that overexpression of GH in the CNS differentiates the effect of GH on body fat mass from that on appetite. The transgenic mice were not GH-deficient but were obese and showed increased food intake as well as increased hypothalamic expression of agouti-related protein and neuropeptide Y. GH also had an acute effect on food intake following intracerebroventricular injection of C57BL/6 mice. The transgenic mice were severely hyperinsulinemic and showed a marked hyperplasia of the islets of Langerhans. In addition, the transgenic mice displayed alterations in serum lipid and lipoprotein levels and hepatic gene expression. In conclusion, GH overexpression in the CNS results in hyperphagia-induced obesity indicating a dual effect of GH with a central stimulation of appetite and a peripheral lipolytic effect.
Address correspondence and reprint requests to Mohammad Bohlooly, Astra Zeneca Transgenics and Comparative Genomics, AstraZeneca Research and Development, 43183 Mölndal, Sweden. E-mail: mohammad.bohlooly{at}astrazeneca.com
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