Depleted Leukocyte Mitochondrial DNA Copy Number in Metabolic Syndrome

Huang, Ching-Hui; Su, Shih‐Li; Hsieh, Ming‐Chia; Cheng, Wen-Ling; Chang, Chia‐Chu; Wu, Hsi-Lin; Kuo, Chen‐Ling; Lin, Ta-Tsung; Liu, Chin‐San

doi:10.5551/jat.8698

Cited by 50 publications

(37 citation statements)

References 30 publications

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“…In this cross-sectional study, we have used a stepwise multiple regression analysis, adjusting for potential confounders such as age,15) BMI,16) and various cardio-metabolic parameters,1718) to show that postmenopausal women who partake in regular exercise have a significantly higher leukocyte mtDNA copy number than postmenopausal women who do not exercise.…”

Section: Discussionmentioning

confidence: 99%

“…An independent association between leukocyte mtDNA copy number and exercise was confirmed using a stepwise multiple linear regression model with a significance threshold of 0.15. Potential confounding variables were defined as those that were significantly associated (P<0.1) with leukocyte mtDNA copy number using Pearson's correlation analysis, either in this study (triglyceride, WHR, waist circumference, and homocysteine level), or in previously reported studies (age,15) BMI,16) systolic and diastolic blood pressure, HOMA-IR, and levels of triglyceride and HDL cholesterol1718)). Multicollinearity between independent variables was evaluated using Pearson's correlation coefficients.…”

Section: Methodsmentioning

confidence: 99%

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Association between Leukocyte Mitochondrial DNA Copy Number and Regular Exercise in Postmenopausal Women

et al. 2016

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BackgroundPrevious studies suggest that habitual exercise can improve skeletal mitochondrial function; however, to date, the association between exercise and mitochondrial function in peripheral leukocytes has not been reported. The aim of this study was to evaluate the relationship between regular exercise and mitochondrial function by measuring leukocyte mitochondrial DNA (mtDNA) copy number in postmenopausal women.MethodsThis cross-sectional study included 144 relatively healthy, non-diabetic, non-smoking, postmenopausal women. Clinical parameters, including anthropometric measurements and cardio-metabolic parameters, were assessed. Regular exercise was defined as at least 150 minutes per week of moderate-intensity activity, or an equivalent combination of moderate and vigorous-intensity activity, over a duration of at least 6 months. Leukocyte mtDNA copy numbers were measured using real-time polymerase chain reaction assays, and these were normalized to the β-globin copy number to give the relative mtDNA copy number.ResultsThe mtDNA copy number of peripheral leukocytes was significantly greater in the exercise group (1.33±0.02) than in the no exercise group (1.05±0.02, P<0.01). Stepwise multiple regression analysis showed that regular exercise was independently associated with mtDNA copy number (β=0.25, P<0.01) after adjusting for the variables age, body mass index, waist-to-hip ratio, systolic and diastolic blood pressure, homeostasis model assessment of insulin resistance value, and levels of high-density lipoprotein cholesterol, triglycerides, and homocysteine.ConclusionRegular exercise is associated with greater leukocyte mtDNA copy number in postmenopausal women.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Association between Leukocyte Mitochondrial DNA Copy Number and Regular Exercise in Postmenopausal Women

et al. 2016

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“…Since Mt/N increased with age in our study, as does the prevalence of impaired glucose tolerance (42), this inverse correlation was unexpected. However, adults with metabolic syndrome with insulin resistance were reported to have lower mitochondrial content in leukocytes (17). …”

Section: Discussionmentioning

confidence: 99%

Increased mitochondrial DNA deletions and copy number in transfusion-dependent thalassemia

Lal¹,

Gómez²,

Calloway³

2016

JCI Insight

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BACKGROUND Iron overload is the primary cause of morbidity in transfusion-dependent thalassemia. Increase in iron causes mitochondrial dysfunction under experimental conditions, but the occurrence and significance of mitochondrial damage is not understood in patients with thalassemia. METHODS Mitochondrial DNA (mtDNA) to nuclear DNA copy number (Mt/N) and frequency of the common 4977-bp mitochondrial deletion (ΔmtDNA4977) were quantified using a quantitative PCR assay on whole blood samples from 38 subjects with thalassemia who were receiving regular transfusions. RESULTS Compared with healthy controls, Mt/N and ΔmtDNA4977 frequency were elevated in thalassemia (P = 0.038 and P < 0.001, respectively). ΔmtDNA4977 was increased in the presence of either liver iron concentration > 15 mg/g dry-weight or splenectomy, with the highest levels observed in subjects who had both risk factors (P = 0.003). Myocardial iron (MRI T2* < 20 ms) was present in 0%, 22%, and 46% of subjects with ΔmtDNA4977 frequency < 20, 20–40, and > 40/1 × 107 mtDNA, respectively (P = 0.025). Subjects with Mt/N values below the group median had significantly lower Matsuda insulin sensitivity index (5.76 ± 0.53) compared with the high Mt/N group (9.11 ± 0.95, P = 0.008). CONCLUSION Individuals with transfusion-dependent thalassemia demonstrate age-related increase in mtDNA damage in leukocytes. These changes are markedly amplified by splenectomy and are associated with extrahepatic iron deposition. Elevated mtDNA damage in blood cells may predict the risk of iron-associated organ damage in thalassemia.

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“…[29,30], insulin resistance [7,31], diabetes mellitus [8,11], increased oxidative stress [32,33], inflammatory reactions [34,35] as well as mutations on genetic levels [36][37][38], of which the risks rise proportionally associated with MSC.…”

Section: Resultsmentioning

confidence: 99%

Utilizing the metabolic syndrome component count in workers’ health surveillance: An example of day-time vs. day-night rotating shift workers

Lin¹,

Hsieh²,

Chen³

2015

Int J Occup Med Environ Health

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Objectives: To establish a practical method for assessing the general metabolic health conditions among different employee groups, this study utilized the total count of metabolic syndrome (MetS) elements as a parameter, and performed a retrospective analysis comparing changes of MetS component count (MSC) of 5 years among day-time work (DW) and day-andnight rotating shift work (RSW) employees. Material and Methods: The data of personal histories, physical examinations, blood tests, abdominal sonographic examinations and occupational records were collected from a cohort of workers in an electronics manufacturing company. We first defined the arithmetic mean value of MSC as MSC density (MSCD) for the employee group; then we compared the changes of MSCD over 5 years between DW and RSW workers. Occupational, personal and health records were analyzed for the 1077 workers with an initial mean age of 32.4 years (standard deviation (SD): 6.2 years), including 565 RSW workers (52%). Results: The initial MSCDs were 1.26 and 1.12 (p = 0.06) for DW and RSW workers, respectively; after 5 years, the increments of MSCD for DW and RSW workers were 0.10 and 0.39, respectively (p < 0.01). By performing multivariate logistic regression analyses, and comparing with DW co-workers, final results indicated that the workers exposed to RSW have 1.7-fold increased risk of elevated MSCD (95% confidence interval (CI): 1.28-2.25, p < 0.01); and are 38% less likely (adjusted rate ratio (aRR) 0.62, 95% CI: 0.45-0.86, p < 0.01) to attain decreased MSCD. Conclusions: These observations demonstrate that changes of MSCD are significantly different between DW and RSW workers, and are increasingly associated with RSW exposure. In conclusion, MSCD can represent the general metabolic health conditions of a given employee group; MSC, MSCD and their transitional changes can be applied as simple and standardized tools for monitoring metabolic health risk profiles when managing employee health, at both the individual and company levels.

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Depleted Leukocyte Mitochondrial DNA Copy Number in Metabolic Syndrome

Cited by 50 publications

References 30 publications

Association between Leukocyte Mitochondrial DNA Copy Number and Regular Exercise in Postmenopausal Women

Association between Leukocyte Mitochondrial DNA Copy Number and Regular Exercise in Postmenopausal Women

Increased mitochondrial DNA deletions and copy number in transfusion-dependent thalassemia

Utilizing the metabolic syndrome component count in workers’ health surveillance: An example of day-time vs. day-night rotating shift workers

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