Journal article
Mitochondrial-nuclear genome interactions in non-alcoholic fatty liver disease in mice
Biochemical journal, Vol.461(2), pp.223-232
07/15/2014
DOI: 10.1042/BJ20131433
PMCID: PMC4086355
PMID: 24758559
Abstract
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 wildtype 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 wildtype 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 mitochondria] and nuclear genomes and support the concept that mtDNA influences mitochondrial function and metabolic pathways implicated in NAFLD.
Details
- Title: Subtitle
- Mitochondrial-nuclear genome interactions in non-alcoholic fatty liver disease in mice
- Creators
- Angela M. Betancourt - University of Alabama at BirminghamAdrienne L. King - University of Alabama at BirminghamJessica L. Fetterman - University of Alabama at BirminghamTelisha Millender-Swain - University of Alabama at BirminghamRachel D. Finley - University of Alabama at BirminghamClaudia R. Oliva - University of Alabama at BirminghamDavid R. Crowe - University of Alabama at BirminghamScott W. Ballinger - University of Alabama at BirminghamShannon M. Bailey - University of Alabama at Birmingham
- Resource Type
- Journal article
- Publication Details
- Biochemical journal, Vol.461(2), pp.223-232
- Publisher
- Portland Press Ltd
- DOI
- 10.1042/BJ20131433
- PMID
- 24758559
- PMCID
- PMC4086355
- ISSN
- 0264-6021
- eISSN
- 1470-8728
- Number of pages
- 10
- Grant note
- AA015172; AA018841; HL094518; HL0103859 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA PRE2240046 / American Heart Association W81XWH-07-1-0540d / US Army Medical Research & Material Command; U.S. Army Medical Research & Materiel Command (USAMRMC) R01HL094518 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) P30DK079626 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) R01AA015172 / NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Alcohol Abuse & Alcoholism (NIAAA)
- Language
- English
- Date published
- 07/15/2014
- Academic Unit
- Radiation Oncology
- Record Identifier
- 9984313080502771
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