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Growth Hormone Control of Hepatic Lipid Metabolism
In humans, low levels of growth hormone (GH) and its mediator, IGF-1, associate with hepatic lipid accumulation. In mice, congenital liver-specific ablation of the GH receptor (GHR) results in reductions in circulating IGF-1 and hepatic steatosis, associated with systemic insulin resistance. Due to...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5127251/ https://www.ncbi.nlm.nih.gov/pubmed/27679560 http://dx.doi.org/10.2337/db16-0649 |
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author | Liu, Zhongbo Cordoba-Chacon, Jose Kineman, Rhonda D. Cronstein, Bruce N. Muzumdar, Radhika Gong, Zhenwei Werner, Haim Yakar, Shoshana |
author_facet | Liu, Zhongbo Cordoba-Chacon, Jose Kineman, Rhonda D. Cronstein, Bruce N. Muzumdar, Radhika Gong, Zhenwei Werner, Haim Yakar, Shoshana |
author_sort | Liu, Zhongbo |
collection | PubMed |
description | In humans, low levels of growth hormone (GH) and its mediator, IGF-1, associate with hepatic lipid accumulation. In mice, congenital liver-specific ablation of the GH receptor (GHR) results in reductions in circulating IGF-1 and hepatic steatosis, associated with systemic insulin resistance. Due to the intricate relationship between GH and IGF-1, the relative contribution of each hormone to the development of hepatic steatosis is unclear. Our goal was to dissect the mechanisms by which hepatic GH resistance leads to steatosis and overall insulin resistance, independent of IGF-1. We have generated a combined mouse model with liver-specific ablation of GHR in which we restored liver IGF-1 expression via the hepatic IGF-1 transgene. We found that liver GHR ablation leads to increases in lipid uptake, de novo lipogenesis, hyperinsulinemia, and hyperglycemia accompanied with severe insulin resistance and increased body adiposity and serum lipids. Restoration of IGF-1 improved overall insulin sensitivity and lipid profile in serum and reduced body adiposity, but was insufficient to protect against steatosis-induced hepatic inflammation or oxidative stress. We conclude that the impaired metabolism in states of GH resistance results from direct actions of GH on lipid uptake and de novo lipogenesis, whereas its actions on extrahepatic tissues are mediated by IGF-1. |
format | Online Article Text |
id | pubmed-5127251 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-51272512017-12-01 Growth Hormone Control of Hepatic Lipid Metabolism Liu, Zhongbo Cordoba-Chacon, Jose Kineman, Rhonda D. Cronstein, Bruce N. Muzumdar, Radhika Gong, Zhenwei Werner, Haim Yakar, Shoshana Diabetes Metabolism In humans, low levels of growth hormone (GH) and its mediator, IGF-1, associate with hepatic lipid accumulation. In mice, congenital liver-specific ablation of the GH receptor (GHR) results in reductions in circulating IGF-1 and hepatic steatosis, associated with systemic insulin resistance. Due to the intricate relationship between GH and IGF-1, the relative contribution of each hormone to the development of hepatic steatosis is unclear. Our goal was to dissect the mechanisms by which hepatic GH resistance leads to steatosis and overall insulin resistance, independent of IGF-1. We have generated a combined mouse model with liver-specific ablation of GHR in which we restored liver IGF-1 expression via the hepatic IGF-1 transgene. We found that liver GHR ablation leads to increases in lipid uptake, de novo lipogenesis, hyperinsulinemia, and hyperglycemia accompanied with severe insulin resistance and increased body adiposity and serum lipids. Restoration of IGF-1 improved overall insulin sensitivity and lipid profile in serum and reduced body adiposity, but was insufficient to protect against steatosis-induced hepatic inflammation or oxidative stress. We conclude that the impaired metabolism in states of GH resistance results from direct actions of GH on lipid uptake and de novo lipogenesis, whereas its actions on extrahepatic tissues are mediated by IGF-1. American Diabetes Association 2016-12 2016-09-27 /pmc/articles/PMC5127251/ /pubmed/27679560 http://dx.doi.org/10.2337/db16-0649 Text en © 2016 by the American Diabetes Association. http://www.diabetesjournals.org/content/licenseReaders may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license. |
spellingShingle | Metabolism Liu, Zhongbo Cordoba-Chacon, Jose Kineman, Rhonda D. Cronstein, Bruce N. Muzumdar, Radhika Gong, Zhenwei Werner, Haim Yakar, Shoshana Growth Hormone Control of Hepatic Lipid Metabolism |
title | Growth Hormone Control of Hepatic Lipid Metabolism |
title_full | Growth Hormone Control of Hepatic Lipid Metabolism |
title_fullStr | Growth Hormone Control of Hepatic Lipid Metabolism |
title_full_unstemmed | Growth Hormone Control of Hepatic Lipid Metabolism |
title_short | Growth Hormone Control of Hepatic Lipid Metabolism |
title_sort | growth hormone control of hepatic lipid metabolism |
topic | Metabolism |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5127251/ https://www.ncbi.nlm.nih.gov/pubmed/27679560 http://dx.doi.org/10.2337/db16-0649 |
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