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https://hdl.handle.net/2440/60797
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Type: | Journal article |
Title: | The asparaginyl hydroxylase factor inhibiting HIF-1α is an essential regulator of metabolism |
Other Titles: | The asparaginyl hydroxylase factor inhibiting HIF-1alpha is an essential regulator of metabolism |
Author: | Zhang, N. Fu, Z. Karttunen, S. Chicher, J. Gorman, J. Visk, D. Haddad, G. Poellinger, L. Peet, D. Powell, F. Johnson, R. |
Citation: | Cell Metabolism, 2010; 11(5):364-378 |
Publisher: | Cell Press |
Issue Date: | 2010 |
ISSN: | 1550-4131 1932-7420 |
Statement of Responsibility: | Na Zhang, Zhenxing Fu, Sarah Linke, Johana Chicher, Jeffrey J. Gorman, DeeAnn Visk, Gabriel G. Haddad, Lorenz Poellinger, Daniel J. Peet, Frank Powell, Randall S. Johnson |
Abstract: | Factor inhibiting HIF-1α (FIH) is an asparaginyl hydroxylase. Hydroxylation of HIF-α proteins by FIH blocks association of HIFs with the transcriptional coactivators CBP/p300, thus inhibiting transcriptional activation. We have created mice with a null mutation in the FIH gene and found that it has little or no discernable role in mice in altering classical aspects of HIF function, e.g., angiogenesis, erythropoiesis, or development. Rather, it is an essential regulator of metabolism: mice lacking FIH exhibit reduced body weight, elevated metabolic rate, hyperventilation, and improved glucose and lipid homeostasis and are resistant to high-fat-diet-induced weight gain and hepatic steatosis. Neuron-specific loss of FIH phenocopied some of the major metabolic phenotypes of the global null animals: those mice have reduced body weight, increased metabolic rate, and enhanced insulin sensitivity and are also protected against high-fat-diet-induced weight gain. These results demonstrate that FIH acts to a significant degree through the nervous system to regulate metabolism. |
Keywords: | Animals Mice, Knockout Mice Fatty Liver Hyperventilation Weight Gain Insulin Mixed Function Oxygenases Glucose Dietary Fats Asparagine Lipid Metabolism Hypoxia-Inducible Factor 1, alpha Subunit Transcriptional Activation |
Rights: | Copyright © 2010 Elsevier Inc. All rights reserved. |
DOI: | 10.1016/j.cmet.2010.03.001 |
Published version: | http://dx.doi.org/10.1016/j.cmet.2010.03.001 |
Appears in Collections: | Aurora harvest 5 Molecular and Biomedical Science publications |
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