Leukocyte mitochondrial DNA copy number, anthropometric indices, and weight change in US women

Objectives: To examine the association between leukocyte mitochondrial DNA copy number (mtCN) and different anthropometric indices as well as weight changes; and to compare mtCN and telomere length with respect to their associations with BMI and age. Design: Population based cohort study. Setting: Nurses' Health Study, an ongoing prospective cohort study of 121,700 nurses enrolled in 1976; in 1989-1990 a subset of 32,826 women provided blood samples. Participants: 1,700 disease-free US women from case-control studies nested within the Nurses' Health Study with mtCN and telomere length measured who also have anthropometric measurements. Main outcome measure: Relative mtCN and telomere lengths in peripheral blood leukocytes measured by quantitative real time polymerase chain reaction and various anthropometric measurements data from initial questionnaire. Results: Leukocyte mtCN was inversely associated with current weight (LS means Q1-Q4: 0.07, 0.04, 0.03, -0.17; P-trend = 0.002), waist size (LS means Q1-Q4: 0.06, 0.05, -0.04, -0.06; P-trend = 0.04), BMI (LS means normal light, normal heavy, overweight, pre-obese, obese: 0.11, -0.01, -0.04, 0.04, -0.25; P-trend < 0.0001), and waist-hip ratio (WHR) (LS means Q1-Q4: 0.06, 0.08, -0.04, -0.06; P-trend = 0.03). A one-unit decrease in mtCN z score was equivalent to approximately 3.5 pounds of weight gain for an adult of 5'10 ''. In addition, weight gain was bi-directionally and inversely associated with mtCN. Moreover, mtCN was strongly positively correlated with telomere length (LS means Q1-Q4: -0.02, 0.09, 0.11, 0.33; P-trend < 0.0001). MtCN was inversely associated with BMI even after adjusting for telomere length (P (trend) = 0.003), while telomere length was not associated with BMI. On the other hand, telomere length was inversely associated with age after adjusting for mtCN (P-trend = 0.04), while mtCN was not associated with age. Conclusions: Our results provide compelling evidence for a potential bi-directional temporal relationship between mitochondrial-mediated oxidative stress-defense mechanisms and weight change.