Ali Hira, Zmuda Joseph M, Cvejkus Ryan K, Kershaw Erin E, Kuipers Allison L, Oczypok Elizabeth A, Wheeler Victor, Bunker Clareann H, Miljkovic Iva
Division of Endocrinology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania.
J Endocr Soc. 2019 Jan 3;3(2):488-495. doi: 10.1210/js.2018-00325. eCollection 2019 Feb 1.
Emerging evidence indicates that ectopic skeletal muscle adiposity may be a risk factor for type 2 diabetes (T2D), especially in persons of African ancestry. studies suggest that a Wnt pathway inhibitor, Dickkopf-related protein 1 (DKK1), plays a role in adiposity regulation and could be a biomarker for adiposity in humans. The objective of this study was to test whether serum DKK1 levels relate to adiposity measures in a cohort from an African ancestry population at high risk for T2D. Fasting serum DKK1 was measured in a sample of 159 men of African ancestry aged ≥40 years (mean age ± SD, 63.5 ± 8.2 years; mean body mass index, 27.8 ± 4.5 kg/m). Anthropometrics included total-body and trunk adiposity measured by dual-energy x-ray absorptiometry and lower-leg skeletal muscle density measured by CT [which reflects the intramuscular adiposity content (mg/cm)]. Serum DKK1 was positively correlated with BMI ( = 0.20; = 0.01), waist circumference ( = 0.15; = 0.046), DXA total-body adiposity ( = 0.24; = 0.003), and DXA trunk adiposity ( = 0.21; = 0.009), independent of age and height. In addition, serum DKK1 was inversely correlated with skeletal muscle density ( = -0.25; = 0.002), independent of age, BMI, and calf muscle area. No significant correlation was found between serum DKK1 and fasting serum glucose or insulin levels or insulin resistance estimated by homeostasis model assessment. These findings suggest that higher levels of serum DKK1 may be associated with greater overall, central, and ectopic skeletal muscle adiposity. Further studies are needed to unravel the potential role of DKK1 in the regulation of adiposity in humans.
新出现的证据表明，异位骨骼肌脂肪过多可能是2型糖尿病（T2D）的一个危险因素，尤其是在非洲裔人群中。研究表明，一种Wnt信号通路抑制剂，即 Dickkopf相关蛋白1（DKK1），在脂肪调节中起作用，并且可能是人类肥胖的一个生物标志物。本研究的目的是测试在一个T2D高风险的非洲裔人群队列中，血清DKK1水平是否与肥胖指标相关。对159名年龄≥40岁的非洲裔男性样本（平均年龄±标准差，63.5±8.2岁；平均体重指数，27.8±4.5kg/m²）测定空腹血清DKK1。人体测量指标包括通过双能X线吸收法测量的全身和躯干脂肪量，以及通过CT测量的小腿骨骼肌密度[其反映肌内脂肪含量（mg/cm³）]。血清DKK1与体重指数（r = 0.20；P = 0.01）、腰围（r = 0.15；P = 0.046）、双能X线吸收法测量的全身脂肪量（r = 0.24；P = 0.003）和双能X线吸收法测量的躯干脂肪量（r = 0.21；P = 0.009）呈正相关，且独立于年龄和身高。此外，血清DKK1与骨骼肌密度呈负相关（r = -0.25；P = 0.002），且独立于年龄、体重指数和小腿肌肉面积。血清DKK1与空腹血糖或胰岛素水平或通过稳态模型评估估计的胰岛素抵抗之间未发现显著相关性。这些发现表明，较高水平的血清DKK1可能与更大程度的总体、中心和异位骨骼肌脂肪过多有关。需要进一步研究以阐明DKK1在人类脂肪调节中的潜在作用。
