Liver Mitochondrial DNA Copy Number and Deletion Levels May Contribute to Nonalcoholic Fatty Liver Disease Susceptibility

Kamfar, Sharareh; Alavian, Seyed Moayed; Houshmand, Massoud; Yadegarazari, Reza; Zarei, Bahram Seifi; Khalaj, Alireza; Shabab, Nooshin; Saidijam, Massoud

doi:10.5812/hepatmon.40774

Cited by 26 publications

(27 citation statements)

References 40 publications

(46 reference statements)

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“…Our findings of increased mitochondrial DNA copy numbers in the NAFLD patients and its positive correlations with oxidants (TBARS) may represent a compensatory response to a heightened oxidative injury. Similar to our results, Kamfar S et al found increased mtDNA copy number associated with NAFLD when comparing 43 Iranian obese NAFLD patients (BMI~44) with 20 obese control subjects (BMI~34) [ 22 ]. However, their report showed a much higher increase in mtDNA copy number (3.7-fold, compared to obese control) than our study (58%, compared to non-NAFLD HD patients).…”

Section: Discussionsupporting

confidence: 90%

“…Mitochondria perform key cellular functions in fat and energy homeostasis through free fatty acid oxidation, electron transfer, and production of ATP and reactive oxygen species [ 21 ]. Disruption of fatty acid oxidation and excessive oxidative stress may be associated with mitochondrial dysfunction, leading to lipid accumulation [ 22 ]. Moreover, mitochondria and their DNA are the main targets of free radicals and are susceptible to oxidative damage [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

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Oxidative Stress and Nonalcoholic Fatty Liver Disease in Hemodialysis Patients

Chen

Lee

et al. 2018

BioMed Research International

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Introduction Nonalcoholic fatty liver disease (NAFLD) is becoming more common around the world and it may progress to cirrhosis and liver failure, increasing mortality risk. In hemodialysis (HD) patients, NAFLD may be a novel risk factor for their high cardiovascular mortality. Heightened oxidative stress is highly prevalent in HD patients. However, the relationship between oxidative stress and NAFLD in HD patients is not well defined. Methods We studied seventy-one stable nondiabetic HD patients. Nineteen patients had the diagnosis of NAFLD by ultrasonography. Blood levels of oxidative stress markers were measured in each patient, including thiobarbituric acid reactive substances (TBARS), free thiols, superoxide dismutase (SOD) activities, and glutathione peroxidase (GPx) activity. The copy numbers of mitochondrial DNA (mtDNA) in peripheral leukocytes were also determined. Demographic, biochemistry, and hemogram data were recorded. The two groups of patients were compared in order to determine the factors associated with NAFLD in HD patients. Findings Compared to those without NAFLD, nondiabetic HD patients with NAFLD had significantly higher mtDNA copy number and GPx levels. The two groups did not differ significantly in dialysis adequacy, hemoglobin, serum calcium, phosphorus, albumin, liver function tests, or lipid profiles. Regression analysis confirmed mtDNA copy numbers and GPx levels as two independent factors associated with NAFLD. Compared to those with polysulfone, patients dialyzed with cellulose membrane have significantly higher levels of TBARS. However, patients with or without NAFLD did not differ in their use of either dialysis membrane. Discussion Oxidative stress (represented by antioxidant defense, GPx) and mitochondrial DNA copy numbers are independently associated with fatty liver disease in nondiabetic HD patients. The diagnostic and therapeutic implications of this key observation warrant further exploration.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Oxidative Stress and Nonalcoholic Fatty Liver Disease in Hemodialysis Patients

Chen

Lee

et al. 2018

BioMed Research International

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“…MtDNA copy number is a measure of mitochondrial function and reflects oxidant-induced cell damage 13 . The relative mtDNA copy number is approximately 3.7-fold higher in patients with non-alcoholic fatty liver disease than in healthy subjects 14 . Defective mtDNA replication can accelerate aging and reduce the lifespan of mice 15 .…”

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confidence: 93%

The distinct spatiotemporal distribution and effect of feed restriction on mtDNA copy number in broilers

Zhang

Wang

et al. 2020

Sci Rep

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Mitochondrial DNA (mtDNA) copy number reflects the abundance of mitochondria in cells and is dependent on the energy requirements of tissues. We hypothesized that the mtDNA copy number in poultry may change with age and tissue, and feed restriction may affect the growth and health of poultry by changing mtDNA content in a tissue-specific pattern. TaqMan real-time PCR was used to quantify mtDNA copy number using three different segments of the mitochondrial genome (D-loop, ATP6, and ND6) relative to the nuclear single-copy preproglucagon gene (GCG). The effect of sex, age, and dietary restriction (quantitative, energy, and protein restriction) on mtDnA copy number variation in the tissues of broilers was investigated. We found that mtDNA copy number varied among tissues (P < 0.01) and presented a distinct change in spatiotemporal pattern. After hatching, the number of mtDNA copies significantly decreased with age in the liver and increased in muscle tissues, including heart, pectoralis, and leg muscles. Newborn broilers (unfed) and embryos (E 11 and E 17) had similar mtDNA contents in muscle tissues. Among 42 d broilers, females had a higher mtDNA copy number than males in the tissues examined. Feed restriction (8-21 d) significantly reduced the body weight but did not significantly change the mtDNA copy number of 21 d broilers. After three weeks of compensatory growth (22-42 d), only the body weight of broilers with a quantitatively restricted diet remained significantly lower than that of broilers in the control group (P < 0.05), while any type of early feed restriction significantly reduced the mtDNA copy number in muscle tissues of 42 d broilers. In summary, the mtDNA copy number of broilers was regulated in a tissue-and age-specific manner. A similar pattern of spatiotemporal change in response to early feed restriction was found in the mtDNA content of muscle tissues, including cardiac and skeletal muscle, whereas liver mtDNA content changed differently with age and dietary restriction. It seems that early restrictions in feed could effectively lower the mtDNA content in muscle cells to reduce the tissue overload in broilers at 42 d to some degree.

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“…Nevertheless, studies on the association of NAFLD with liver mtDNAcn were contradictory. For instance, increased liver mtDNAcn has been reported in mice and patients with NAFLD (15,16), whereas another study indicated that liver mtDNAcn was decreased in patients with NAFLD (17). A previous study has indicated that the mtDNAcn of leukocytes is well-related to that in the rat liver (18), but the studies on the association between leukocyte mtDNAcn and NAFLD are Abbreviations: mtDNAcn, mitochondrial DNA copy number; NAFLD, nonalcoholic fatty liver disease; TNF-α, tumor necrosis factor α; IL-6, interleukin 6; GR, glutathione reductase; SOD, superoxide dismutase; 8-oxo-dG, 8-oxo-2 ′deoxyguanosine; NASH, non-alcoholic steatohepatitis; WC, waist circumference; AGT, abnormal glucose tolerance; NGT, normal glucose tolerance; HbA 1c , hemoglobin A 1c ; HOMA-IR, Homeostatic Model Assessment of Insulin Resistance; ALT, alanine transaminase; AST, aspartate transaminase; UA, uric acid; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; TC, cholesterol; TG, triglyceride.…”

Section: Introductionmentioning

confidence: 99%