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Mitochondrial ATP transporter depletion protects mice against liver steatosis and insulin resistance
Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disorder in obese individuals. Adenine nucleotide translocase (ANT) exchanges ADP/ATP through the mitochondrial inner membrane, and Ant2 is the predominant isoform expressed in the liver. Here we demonstrate that targeted disruption of...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5316896/ https://www.ncbi.nlm.nih.gov/pubmed/28205519 http://dx.doi.org/10.1038/ncomms14477 |
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author | Cho, Joonseok Zhang, Yujian Park, Shi-Young Joseph, Anna-Maria Han, Chul Park, Hyo-Jin Kalavalapalli, Srilaxmi Chun, Sung-Kook Morgan, Drake Kim, Jae-Sung Someya, Shinichi Mathews, Clayton E. Lee, Young Jae Wohlgemuth, Stephanie E. Sunny, Nishanth E. Lee, Hui-Young Choi, Cheol Soo Shiratsuchi, Takayuki Oh, S. Paul Terada, Naohiro |
author_facet | Cho, Joonseok Zhang, Yujian Park, Shi-Young Joseph, Anna-Maria Han, Chul Park, Hyo-Jin Kalavalapalli, Srilaxmi Chun, Sung-Kook Morgan, Drake Kim, Jae-Sung Someya, Shinichi Mathews, Clayton E. Lee, Young Jae Wohlgemuth, Stephanie E. Sunny, Nishanth E. Lee, Hui-Young Choi, Cheol Soo Shiratsuchi, Takayuki Oh, S. Paul Terada, Naohiro |
author_sort | Cho, Joonseok |
collection | PubMed |
description | Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disorder in obese individuals. Adenine nucleotide translocase (ANT) exchanges ADP/ATP through the mitochondrial inner membrane, and Ant2 is the predominant isoform expressed in the liver. Here we demonstrate that targeted disruption of Ant2 in mouse liver enhances uncoupled respiration without damaging mitochondrial integrity and liver functions. Interestingly, liver specific Ant2 knockout mice are leaner and resistant to hepatic steatosis, obesity and insulin resistance under a lipogenic diet. Protection against fatty liver is partially recapitulated by the systemic administration of low-dose carboxyatractyloside, a specific inhibitor of ANT. Targeted manipulation of hepatic mitochondrial metabolism, particularly through inhibition of ANT, may represent an alternative approach in NAFLD and obesity treatment. |
format | Online Article Text |
id | pubmed-5316896 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-53168962017-02-27 Mitochondrial ATP transporter depletion protects mice against liver steatosis and insulin resistance Cho, Joonseok Zhang, Yujian Park, Shi-Young Joseph, Anna-Maria Han, Chul Park, Hyo-Jin Kalavalapalli, Srilaxmi Chun, Sung-Kook Morgan, Drake Kim, Jae-Sung Someya, Shinichi Mathews, Clayton E. Lee, Young Jae Wohlgemuth, Stephanie E. Sunny, Nishanth E. Lee, Hui-Young Choi, Cheol Soo Shiratsuchi, Takayuki Oh, S. Paul Terada, Naohiro Nat Commun Article Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disorder in obese individuals. Adenine nucleotide translocase (ANT) exchanges ADP/ATP through the mitochondrial inner membrane, and Ant2 is the predominant isoform expressed in the liver. Here we demonstrate that targeted disruption of Ant2 in mouse liver enhances uncoupled respiration without damaging mitochondrial integrity and liver functions. Interestingly, liver specific Ant2 knockout mice are leaner and resistant to hepatic steatosis, obesity and insulin resistance under a lipogenic diet. Protection against fatty liver is partially recapitulated by the systemic administration of low-dose carboxyatractyloside, a specific inhibitor of ANT. Targeted manipulation of hepatic mitochondrial metabolism, particularly through inhibition of ANT, may represent an alternative approach in NAFLD and obesity treatment. Nature Publishing Group 2017-02-16 /pmc/articles/PMC5316896/ /pubmed/28205519 http://dx.doi.org/10.1038/ncomms14477 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Cho, Joonseok Zhang, Yujian Park, Shi-Young Joseph, Anna-Maria Han, Chul Park, Hyo-Jin Kalavalapalli, Srilaxmi Chun, Sung-Kook Morgan, Drake Kim, Jae-Sung Someya, Shinichi Mathews, Clayton E. Lee, Young Jae Wohlgemuth, Stephanie E. Sunny, Nishanth E. Lee, Hui-Young Choi, Cheol Soo Shiratsuchi, Takayuki Oh, S. Paul Terada, Naohiro Mitochondrial ATP transporter depletion protects mice against liver steatosis and insulin resistance |
title | Mitochondrial ATP transporter depletion protects mice against liver steatosis and insulin resistance |
title_full | Mitochondrial ATP transporter depletion protects mice against liver steatosis and insulin resistance |
title_fullStr | Mitochondrial ATP transporter depletion protects mice against liver steatosis and insulin resistance |
title_full_unstemmed | Mitochondrial ATP transporter depletion protects mice against liver steatosis and insulin resistance |
title_short | Mitochondrial ATP transporter depletion protects mice against liver steatosis and insulin resistance |
title_sort | mitochondrial atp transporter depletion protects mice against liver steatosis and insulin resistance |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5316896/ https://www.ncbi.nlm.nih.gov/pubmed/28205519 http://dx.doi.org/10.1038/ncomms14477 |
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