The relationship between leukocyte mitochondrial DNA contents and metabolic syndrome in postmenopausal women.
ABSTRACT Menopause is associated with increased risk of metabolic syndrome. There is growing evidence that mitochondrial dysfunction may lead to obesity and insulin resistance, which are major components of metabolic syndrome. The purpose of this study was to illuminate the relationship between mitochondrial function using leukocyte mitochondrial DNA copy number and metabolic syndrome in postmenopausal women.
The present study included 144 postmenopausal women. Women with cardiovascular disease were excluded from the study sample. Anthropometric evaluation and biochemical tests were performed. Leukocyte mitochondrial DNA copy numbers were then measured.
The levels of leukocyte mitochondrial DNA copy number were lower among participants with metabolic syndrome than among those without metabolic syndrome (P < 0.01). As the number of components of metabolic syndrome increased, the concentration of leukocyte mitochondrial DNA copy number decreased (P = 0.02). Leukocyte mitochondrial DNA copy number was negatively correlated with waist circumference (r = -0.19, P = 0.03), fasting insulin (r = -0.19, P = 0.03), total cholesterol (r = -0.22, P < 0.01), and triglyceride (r = -0.37, P < 0.01). Leukocyte mitochondrial DNA copy number was positively associated with serum 25-hydroxyvitamin D levels (r = 0.94, P = <0.01). Multiple logistic regression analysis showed that leukocyte mitochondrial DNA copy number (odds ratio, 0.030; 95% CI, 0.002-0.437, P = 0.01) was independently associated with metabolic syndrome after adjustment for potential confounding variables including age, body mass index, homeostasis model assessment of insulin resistance, 25-hydroxyvitamin D, adiponectin, and high-sensitivity C-reactive protein.
Leukocyte mitochondrial DNA copy number was independently associated with metabolic syndrome in postmenopausal women.
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ABSTRACT: Mitochondria are the product of an ancient endosymbiotic event between an alpha-proteobacterium and an archael host. An early barrier to overcome in this relationship was the control of the bacterium's proliferation within the host. Undoubtedly, the bacterium (or protomitochondrion) would have used its own cell division apparatus to divide at first and, today a remnant of this system remains in some "ancient" and diverse eukaryotes such as algae and amoebae, the most conserved and widespread of all bacterial division proteins, FtsZ. In many of the eukaryotes that still use FtsZ to constrict the mitochondria from the inside, the mitochondria still resemble bacteria in shape and size. Eukaryotes, however, have a mitochondrial morphology that is often highly fluid, and in their tubular networks of mitochondria, division is clearly complemented by mitochondrial fusion. FtsZ is no longer used by these complex eukaryotes, and may have been replaced by other proteins better suited to sustaining complex mitochondrial networks. Although proteins that divide mitochondria from the inside are just beginning to be characterized in higher eukaryotes, many division proteins are known to act on the outside of the organelle. The most widespread of these are the dynamin-like proteins, which appear to have been recruited very early in the evolution of mitochondria. The essential nature of mitochondria dictates that their loss is intolerable to human cells, and that mutations disrupting mitochondrial division are more likely to be fatal than result in disease. To date, only one disease (Charcot-Marie-Tooth disease 2A) has been mapped to a gene that is required for mitochondrial division, whereas two other diseases can be attributed to mutations in mitochondrial fusion genes. Apart from playing a role in regulating the morphology, which might be important for efficient ATP production, research has indicated that the mitochondrial division and fusion proteins can also be important during apoptosis; mitochondrial fragmentation is an early triggering (and under many stimuli, essential) step in the pathway to cell suicide.International Review of Cytology 02/2006; 254:151-213. · 6.09 Impact Factor
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ABSTRACT: Women with the metabolic syndrome (central obesity, insulin resistance, and dyslipidemia) are known to be at especially high risk for cardiovascular disease (CVD). The prevalence of the metabolic syndrome increases with menopause and may partially explain the apparent acceleration in CVD after menopause. The transition from pre- to postmenopause is associated with the emergence of many features of the metabolic syndrome, including 1) increased central (intraabdominal) body fat; 2) a shift toward a more atherogenic lipid profile, with increased low density lipoprotein and triglycerides levels, reduced high density lipoprotein, and small, dense low density lipoprotein particles; 3) and increased glucose and insulin levels. The emergence of these risk factors may be a direct result of ovarian failure or, alternatively, an indirect result of the metabolic consequences of central fat redistribution with estrogen deficiency. It is unclear whether the transition to menopause increases CVD risk in all women or only those who develop features of the metabolic syndrome. This article will review the features of the metabolic syndrome that emerge with estrogen deficiency. A better understanding of these metabolic changes with menopause will aid in the recognition and treatment of women at risk for future CVD, leading to appropriate interventions.Journal of Clinical Endocrinology & Metabolism 07/2003; 88(6):2404-11. · 6.43 Impact Factor
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ABSTRACT: Insulin resistance is characteristic of obesity, type 2 diabetes, and components of the cardiometabolic syndrome, including hypertension and dyslipidemia, that collectively contribute to a substantial risk for cardiovascular disease. Metabolic actions of insulin in classic insulin target tissues (eg, skeletal muscle, fat, and liver), as well as actions in nonclassic targets (eg, cardiovascular tissue), help to explain why insulin resistance and metabolic dysregulation are central in the pathogenesis of the cardiometabolic syndrome and cardiovascular disease. Glucose and lipid metabolism are largely dependent on mitochondria to generate energy in cells. Thereby, when nutrient oxidation is inefficient, the ratio of ATP production/oxygen consumption is low, leading to an increased production of superoxide anions. Reactive oxygen species formation may have maladaptive consequences that increase the rate of mutagenesis and stimulate proinflammatory processes. In addition to reactive oxygen species formation, genetic factors, aging, and reduced mitochondrial biogenesis all contribute to mitochondrial dysfunction. These factors also contribute to insulin resistance in classic and nonclassic insulin target tissues. Insulin resistance emanating from mitochondrial dysfunction may contribute to metabolic and cardiovascular abnormalities and subsequent increases in cardiovascular disease. Furthermore, interventions that improve mitochondrial function also improve insulin resistance. Collectively, these observations suggest that mitochondrial dysfunction may be a central cause of insulin resistance and associated complications. In this review, we discuss mechanisms of mitochondrial dysfunction related to the pathophysiology of insulin resistance in classic insulin-responsive tissue, as well as cardiovascular tissue.Circulation Research 03/2008; 102(4):401-14. · 11.86 Impact Factor