NAFLD (non-alcoholic fatty liver disease) involves significant changes in liver metabolism characterized by oxidative stress, lipid accumulation and fibrogenesis. Mitochondrial dysfunction and bioenergetic defects also contribute to NAFLD. In the present study, we examined whether differences in mtDNA influence NAFLD. To determine the role of mitochondrial and nuclear genomes in NAFLD, MNX (mitochondrial–nuclear exchange) mice were fed an atherogenic diet. MNX mice have mtDNA from C57BL/6J mice on a C3H/HeN nuclear background and vice versa. Results from MNX mice were compared with wild-type C57BL/6J and C3H/HeN mice fed a control or atherogenic diet. Mice with the C57BL/6J nuclear genome developed more macrosteatosis, inflammation and fibrosis compared with mice containing the C3H/HeN nuclear genome when fed the atherogenic diet. These changes were associated with parallel alterations in inflammation and fibrosis gene expression in wild-type mice, with intermediate responses in MNX mice. Mice with the C57BL/6J nuclear genome had increased State 4 respiration, whereas MNX mice had decreased State 3 respiration and RCR (respiratory control ratio) when fed the atherogenic diet. Complex IV activity and most mitochondrial biogenesis genes were increased in mice with the C57BL/6J nuclear or mitochondrial genome, or both fed the atherogenic diet. These results reveal new interactions between mitochondrial and nuclear genomes and support the concept that mtDNA influences mitochondrial function and metabolic pathways implicated in NAFLD.
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Research Article|
June 26 2014
Mitochondrial–nuclear genome interactions in non-alcoholic fatty liver disease in mice
Angela M. Betancourt;
Angela M. Betancourt
*Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, U.S.A.
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Adrienne L. King;
Adrienne L. King
†Department of Environmental Health Sciences, University of Alabama at Birmingham, Birmingham, AL, U.S.A.
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Jessica L. Fetterman;
Jessica L. Fetterman
*Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, U.S.A.
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Telisha Millender-Swain;
Telisha Millender-Swain
*Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, U.S.A.
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Rachel D. Finley;
Rachel D. Finley
*Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, U.S.A.
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Claudia R. Oliva;
Claudia R. Oliva
‡Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, AL, U.S.A.
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David R. Crowe;
David R. Crowe
*Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, U.S.A.
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Scott W. Ballinger;
Scott W. Ballinger
1
*Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, U.S.A.
§Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL, U.S.A.
1Correspondence may be addressed to either of these authors (email sballing@uab.edu or sbailey@uab.edu).
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Shannon M. Bailey
Shannon M. Bailey
1
*Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, U.S.A.
†Department of Environmental Health Sciences, University of Alabama at Birmingham, Birmingham, AL, U.S.A.
§Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL, U.S.A.
1Correspondence may be addressed to either of these authors (email sballing@uab.edu or sbailey@uab.edu).
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Publisher: Portland Press Ltd
Received:
October 30 2013
Revision Received:
April 21 2014
Accepted:
April 23 2014
Accepted Manuscript online:
April 23 2014
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2014 Biochemical Society
2014
Biochem J (2014) 461 (2): 223–232.
Article history
Received:
October 30 2013
Revision Received:
April 21 2014
Accepted:
April 23 2014
Accepted Manuscript online:
April 23 2014
Citation
Angela M. Betancourt, Adrienne L. King, Jessica L. Fetterman, Telisha Millender-Swain, Rachel D. Finley, Claudia R. Oliva, David R. Crowe, Scott W. Ballinger, Shannon M. Bailey; Mitochondrial–nuclear genome interactions in non-alcoholic fatty liver disease in mice. Biochem J 15 July 2014; 461 (2): 223–232. doi: https://doi.org/10.1042/BJ20131433
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