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Metabolic Consequences of High-Fat Diet Are Attenuated by Suppression of HIF-1α
Obesity is associated with tissue hypoxia and the up-regulation of hypoxia inducible factor 1 alpha (HIF-1α). Prior studies in transgenic mice have shown that HIF-1α plays a role in the metabolic dysfunction associated with obesity. Therefore, we hypothesized that, after the development of diet-indu...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3462192/ https://www.ncbi.nlm.nih.gov/pubmed/23049707 http://dx.doi.org/10.1371/journal.pone.0046562 |
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author | Shin, Mi-Kyung Drager, Luciano F. Yao, Qiaoling Bevans-Fonti, Shannon Yoo, Doo-Young Jun, Jonathan C. Aja, Susan Bhanot, Sanjay Polotsky, Vsevolod Y. |
author_facet | Shin, Mi-Kyung Drager, Luciano F. Yao, Qiaoling Bevans-Fonti, Shannon Yoo, Doo-Young Jun, Jonathan C. Aja, Susan Bhanot, Sanjay Polotsky, Vsevolod Y. |
author_sort | Shin, Mi-Kyung |
collection | PubMed |
description | Obesity is associated with tissue hypoxia and the up-regulation of hypoxia inducible factor 1 alpha (HIF-1α). Prior studies in transgenic mice have shown that HIF-1α plays a role in the metabolic dysfunction associated with obesity. Therefore, we hypothesized that, after the development of diet-induced obesity (DIO), metabolic function could be improved by administration of HIF-1α antisense oligonucleotides (ASO). DIO mice were treated with HIF-1α ASO or with control ASO for 8 weeks and compared with an untreated group. We found that HIF-1α ASO markedly suppressed Hif-1α gene expression in adipose tissue and the liver. HIF-1α ASO administration induced weight loss. Final body weight was 41.6±1.4 g in the HIF-1α ASO group vs 46.7±0.9 g in the control ASO group and 47.9±0.8 g in untreated mice (p<0.001). HIF-1α ASO increased energy expenditure (13.3±0.6 vs 12±0.1 and 11.9±0.4 kcal/kg/hr, respectively, p<0.001) and decreased the respiratory exchange ratio (0.71±0.01 vs 0.75±0.01 and 0.76±0.01, respectively, p<0.001), which suggested switching metabolism to fat oxidation. In contrast, HIF-1a ASO had no effect on food intake or activity. HIF-1α ASO treatment decreased fasting blood glucose (195.5±8.4 mg/dl vs 239±7.8 mg/dl in the control ASO group and 222±8.2 mg/dl in untreated mice, p<0.01), plasma insulin, hepatic glucose output, and liver fat content. These findings demonstrate that the metabolic consequences of DIO are attenuated by HIF-1α ASO treatment. |
format | Online Article Text |
id | pubmed-3462192 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-34621922012-10-05 Metabolic Consequences of High-Fat Diet Are Attenuated by Suppression of HIF-1α Shin, Mi-Kyung Drager, Luciano F. Yao, Qiaoling Bevans-Fonti, Shannon Yoo, Doo-Young Jun, Jonathan C. Aja, Susan Bhanot, Sanjay Polotsky, Vsevolod Y. PLoS One Research Article Obesity is associated with tissue hypoxia and the up-regulation of hypoxia inducible factor 1 alpha (HIF-1α). Prior studies in transgenic mice have shown that HIF-1α plays a role in the metabolic dysfunction associated with obesity. Therefore, we hypothesized that, after the development of diet-induced obesity (DIO), metabolic function could be improved by administration of HIF-1α antisense oligonucleotides (ASO). DIO mice were treated with HIF-1α ASO or with control ASO for 8 weeks and compared with an untreated group. We found that HIF-1α ASO markedly suppressed Hif-1α gene expression in adipose tissue and the liver. HIF-1α ASO administration induced weight loss. Final body weight was 41.6±1.4 g in the HIF-1α ASO group vs 46.7±0.9 g in the control ASO group and 47.9±0.8 g in untreated mice (p<0.001). HIF-1α ASO increased energy expenditure (13.3±0.6 vs 12±0.1 and 11.9±0.4 kcal/kg/hr, respectively, p<0.001) and decreased the respiratory exchange ratio (0.71±0.01 vs 0.75±0.01 and 0.76±0.01, respectively, p<0.001), which suggested switching metabolism to fat oxidation. In contrast, HIF-1a ASO had no effect on food intake or activity. HIF-1α ASO treatment decreased fasting blood glucose (195.5±8.4 mg/dl vs 239±7.8 mg/dl in the control ASO group and 222±8.2 mg/dl in untreated mice, p<0.01), plasma insulin, hepatic glucose output, and liver fat content. These findings demonstrate that the metabolic consequences of DIO are attenuated by HIF-1α ASO treatment. Public Library of Science 2012-10-01 /pmc/articles/PMC3462192/ /pubmed/23049707 http://dx.doi.org/10.1371/journal.pone.0046562 Text en © 2012 Shin et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Shin, Mi-Kyung Drager, Luciano F. Yao, Qiaoling Bevans-Fonti, Shannon Yoo, Doo-Young Jun, Jonathan C. Aja, Susan Bhanot, Sanjay Polotsky, Vsevolod Y. Metabolic Consequences of High-Fat Diet Are Attenuated by Suppression of HIF-1α |
title | Metabolic Consequences of High-Fat Diet Are Attenuated by Suppression of HIF-1α |
title_full | Metabolic Consequences of High-Fat Diet Are Attenuated by Suppression of HIF-1α |
title_fullStr | Metabolic Consequences of High-Fat Diet Are Attenuated by Suppression of HIF-1α |
title_full_unstemmed | Metabolic Consequences of High-Fat Diet Are Attenuated by Suppression of HIF-1α |
title_short | Metabolic Consequences of High-Fat Diet Are Attenuated by Suppression of HIF-1α |
title_sort | metabolic consequences of high-fat diet are attenuated by suppression of hif-1α |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3462192/ https://www.ncbi.nlm.nih.gov/pubmed/23049707 http://dx.doi.org/10.1371/journal.pone.0046562 |
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