Peripheral blood mitochondrial DNA content correlates with lipid oxidation rate during euglycemic clamps in healthy young men
Introduction
The mitochondrion is the chief site of intracellular respiration and energy metabolism. Qualitative changes in mitochondrial DNA (mtDNA), such as mutations and deletions, have been implicated in the pathogenesis of diabetes mellitus [1], [2], [3], [4]. This can, however, explain only a very small proportion of the patients with diabetes mellitus [5], [6].
In addition to the qualitative changes, mtDNA is subject to quantitative changes [7], [8]. It was recently found that mtDNA content of peripheral blood leukocytes is decreased in the patients with diabetes mellitus[9], the finding of which has been confirmed by another group [10]. It has been suggested that increased oxidative stress in diabetes may be responsible for both qualitative and quantitative changes in mtDNA [9], [10]. However, there is another possibility that decrease in mtDNA content may be involved in the pathogenesis of diabetes rather than a consequence of diabetes, because this decrease preceded the development of diabetes [9]. In fact, mtDNA content correlated with the clinical parameters of insulin resistance syndrome, including diastolic blood pressure and waist-to-hip ratio.
This prompted one to investigate whether there is a correlation between mtDNA content and the biochemical parameters of insulin resistance in non-diabetic subjects. MtDNA content of peripheral blood leukocytes was studied in Korean healthy young men, and this was correlated with various parameters of fuel metabolism at baseline and during euglycemic hyperinsulinemic clamps.
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Subjects
Eleven male medical students were recruited for this study. Their mean age was 22.6 (range, 21–26) years and their mean body mass index (BMI) was 22.2 (range, 17.7–29.4) kg/m2. No subjects had a history of major illness or showed any evidence of systemic disease. They were not taking any medication and there was no history of diabetes mellitus among first-degree relatives. Before their participation, the nature, purpose and possible risks of the study were explained, and all gave written
Correlation between mtDNA content and metabolic parameters at base line
There was no statistically significant correlation between mtDNA content and metabolic parameters such as BMI, WHR and blood pressure (Table 1). Neither basal fat oxidation rates nor carbohydrate oxidation rates were related with mtDNA content.
Correlation between mtDNA content and metabolic parameters during the clamps
As expected, there was a significant increase in cabohydrate oxidation rate (2.97±0.28 vs 1.58±0.26 mg/kg per min, P<0.001) and a significant decrease in fat oxidation rate (0.18±0.10 vs 0.70±0.12 mg/kg per min, P<0.001) during the euglycemic clamps when
Discussion
This study showed for the first time that in healthy young male subjects, the mtDNA content of peripheral blood leukocytes correlated positively with fat oxidation rate during the euglycemic clamps and the decrement of it from the basal state. Similarly, the increment in carbohydrate oxidation rate induced by euglycemic clamps correlated negatively with mtDNA content. Thus, it appears that the higher the mtDNA content, the more fat and the less carbohydrates are used as an energy source in a
Acknowledgements
This paper was supported by a grant from the Korean Ministry of Science and Technology Special Development Research Fund and a grant from Seoul National University Hospital (02-97-007). We are indebted to Dr Chang Hyun Yoon at the Department of Physiology and Biophysics, University of Southern California, for invaluable suggestions.
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2007, Diabetes Research and Clinical PracticeCitation Excerpt :Very interestingly, we also found that the mtDNA copy number was correlated with both insulin resistance and insulin secretory function [6], which suggested that the decreased mtDNA copy number might be responsible for the two major defects in type 2 diabetes: insulin resistance in the peripheral tissue and impaired insulin secretion from pancreatic β cells. Furthermore, in a study of young volunteers [7,8], we found that mtDNA copy number of peripheral blood cells was positively correlated with fat oxidation rate, insulin sensitivity, and insulin secretion. In addition, decreased mtDNA copy number was associated with increased plasma homocystein level, which is known to be a non-traditional risk factor of cardiovascular disease [9].
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