Reduced leukocyte mitochondrial copy number in metabolic syndrome and metabolically healthy obesity

Abstract

ObjectiveThis study aimed to investigate the associations between peripheral blood leukocyte mitochondrial copy number, metabolic syndrome, and adiposity-related body composition phenotypes in a high prevalence population.MethodsA single center cross-sectional study was conducted, consisting of 521 middle-aged subjects of Maltese-Caucasian ethnicity. Participants were stratified according to the presence of metabolic syndrome and different metabolic health definitions based on NCEP-ATP III criteria. Relative leukocyte mitochondrial DNA copy number was determined by quantitative polymerase chain reaction and corrected for leukocyte and platelet count. The associations between mitochondrial copy number and metabolic syndrome components was evaluated and adjusted for age and gender.ResultsSignificant negative correlations between mtDNA copy number and BMI, waist circumference, triglyceride levels, fasting plasma glucose, HbA1c, HOMA-IR and hsCRP were observed, along with a positive correlation with HDL-C levels. Mitochondrial copy number was lower in individuals with metabolic syndrome. When compared to metabolically healthy normal weight subjects, a reduction in mtDNA copy number was observed in both the metabolically healthy and unhealthy obese categories.ConclusionOur data supports the association between reduced leukocyte mtDNA copy number, obesity, and metabolic syndrome. This investigation expands on the spectrum of associations between mtDNA copy number and metabolic phenotypes in different populations and underpins the role of mitochondrial dysfunction in the development and progression of metabolic syndrome and its components.

Inverse associations of cord blood mitochondrial DNA copy number with childhood adiposity

“…Meta-analyses have reported that lower mtDNAcn in peripheral blood was associated with higher BMI, visceral fat area, and waist circumference [17] and increased odds of obesity, hyperlipidemia, and other metabolic syndrome components [9,36]. mtDNAcn in peripheral blood leukocytes was also negatively associated with BMI, waist circumference, and triglyceride levels in nurses and a population of Maltese-Caucasian participants [18,37].…”

“…In adult populations, peripheral blood mtDNAcn is negatively associated with adiposity markers such as BMI, waist circumference, and visceral fat area [17,18]. However, there has been little research investigating the relationship between mitochondrial content and adiposity in children [19,20].…”

Twin pair analysis uncovers novel links between DNA methylation, mitochondrial DNA quantity and obesity

“…The connection between mtDNAq and obesity has been established 10,34,35 , yet the exploration of causal pathways has been limited. We identified a dualistic relationship between mtDNAq and obesity-related outcomes which pointed to either causation from mtDNAq to several obesity-related outcomes or the presence of unmeasured within-individual confounding.…”

Telomere Length and Mitochondrial DNA Copy Number Variations in Patients with Obesity: Effect of Diet-Induced Weight Loss—A Pilot Study

“…A relationship between mitochondrial-mediated oxidative stress-defense mechanisms and weight change has been suggested in a population-based study, by demonstrating that the leukocyte mtDNA copy number is inversely associated with weight, BMI, waist circumference, and waist–hip ratio [ 16 ]. Furthermore, the association between the reduced leukocyte mtDNA copy number, obesity, and metabolic syndrome was widely described in the literature, expanding the spectrum of associations between the mtDNA copy number and metabolic phenotypes in different populations [ 41 ]. Telomere lengths and the mtDNA copy number may be additional markers of the dynamic metabolic homeostasis in patients with obesity.…”