Meng Shasha, Wu Shaowei, Liang Liming, Liang Geyu, Giovannucci Edward, De Vivo Immaculata, Nan Hongmei
Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
Oncotarget. 2016 Sep 13;7(37):60676-60686. doi: 10.18632/oncotarget.10325.
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.
Population based cohort study.
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.
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.
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.
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.
Our results provide compelling evidence for a potential bi-directional temporal relationship between mitochondrial-mediated oxidative stress-defense mechanisms and weight change.
研究白细胞线粒体DNA拷贝数（mtCN）与不同人体测量指标以及体重变化之间的关联；并比较mtCN和端粒长度与体重指数（BMI）和年龄的关联。
基于人群的队列研究。
护士健康研究，一项始于1976年的对121,700名护士进行的正在进行的前瞻性队列研究；在1989 - 1990年，32,826名女性的一个子集提供了血样。
来自护士健康研究中嵌套的病例对照研究的1700名无疾病美国女性，她们测量了mtCN和端粒长度，并且也有人体测量数据。
通过定量实时聚合酶链反应测量的外周血白细胞中相对mtCN和端粒长度，以及来自初始问卷的各种人体测量数据。
白细胞mtCN与当前体重呈负相关（最小二乘均值Q1 - Q4：0.07，0.04，0.03， - 0.17；P趋势 = 0.002），腰围（最小二乘均值Q1 - Q4：0.06，0.05， - 0.04， - 0.06；P趋势 = 0.04），BMI（最小二乘均值正常轻、正常重、超重、肥胖前期、肥胖：0.11， - 0.01， - 0.04，0.04， - 0.25；P趋势<0.0001），以及腰臀比（WHR）（最小二乘均值Q1 - Q4：0.06，0.08， - 0.04， - 0.06；P趋势 = 0.03）。对于身高5英尺10英寸的成年人，mtCN z评分每降低一个单位相当于体重增加约3.5磅。此外，体重增加与mtCN呈双向负相关。而且，mtCN与端粒长度呈强正相关（最小二乘均值Q1 - Q4： - 0.02，0.09 / 0.11，0.33；P趋势<0.0001）。即使在调整端粒长度后，mtCN仍与BMI呈负相关（P趋势 = 0.003），而端粒长度与BMI无关。另一方面，在调整mtCN后，端粒长度与年龄呈负相关（P趋势 = 0.04），而mtCN与年龄无关。
我们的结果为线粒体介导的氧化应激防御机制与体重变化之间潜在的双向时间关系提供了有力证据。
