Department of Pediatrics, Yale School of Medicine, New Haven, CT, USA.
Department of Medicine and Health Sciences, "V. Tiberio," University of Molise, Campobasso, Italy.
Nutr Diabetes. 2022 Feb 22;12(1):9. doi: 10.1038/s41387-022-00187-2.
Growth differentiation factor 15 (GDF15) has been associated with food intake and weight regulation in response to metabolic stress. In animal models, it has been noted that it may play a role in the progression of non-alcoholic fatty liver disease (NAFLD), the leading cause of chronic liver disease in children.
In the current study, we explored the association of circulating plasma concentrations of GDF15 with NAFLD in youth with overweight/obesity, and whether changes in plasma concentrations in GDF15 parallel the changes in intrahepatic fat content (HFF%) over time.
Plasma GDF15 concentrations were measured by ELISA in 175 youth with overweight/obesity who underwent an oral glucose tolerance test (OGTT) and magnetic resonance imaging (MRI) to assess intrahepatic, visceral, and subcutaneous fat. Baseline fasting GDF15 concentrations were measured in twenty-two overweight/obese youth who progressed (n = 11) or regressed (n = 11) in HFF% by more than 30% of original over a 2-year period.
Youth with NAFLD had significantly higher plasma concentrations of GDF15 than those without NAFLD, independent of age, sex, ethnicity, BMI z-score (BMIz), and visceral fat (P = 0.002). During the OGTT, there was a decline in plasma GDF15 concentrations from 0 to 60 min, but GDF15 concentrations returned to basal levels by the end of the study. There was a statistically significant association between change in HFF% and change in GDF15 (P = 0.008; r = 0.288) over ~2 years of follow-up.
These data suggest that plasma GDF15 concentrations change with change in intrahepatic fat content in youth with overweight/obesity and may serve as a biomarker for NAFLD in children.
生长分化因子 15（GDF15）与代谢应激时的食物摄入和体重调节有关。在动物模型中，已经注意到它可能在非酒精性脂肪性肝病（NAFLD）的进展中发挥作用，NAFLD 是儿童慢性肝病的主要原因。
在目前的研究中，我们探讨了超重/肥胖青少年循环血浆 GDF15 浓度与 NAFLD 的相关性，以及 GDF15 血浆浓度的变化是否与肝内脂肪含量（HFF%）随时间的变化平行。
通过酶联免疫吸附试验（ELISA）测量了 175 名超重/肥胖青少年的血浆 GDF15 浓度，这些青少年进行了口服葡萄糖耐量试验（OGTT）和磁共振成像（MRI），以评估肝内、内脏和皮下脂肪。在 22 名超重/肥胖青少年中测量了基线空腹 GDF15 浓度，这些青少年在 2 年内 HFF%增加或减少超过原始值的 30%（n=11）。
NAFLD 青少年的血浆 GDF15 浓度明显高于无 NAFLD 者，独立于年龄、性别、种族、BMI z 评分（BMIz）和内脏脂肪（P=0.002）。在 OGTT 期间，血浆 GDF15 浓度从 0 分钟到 60 分钟下降，但在研究结束时 GDF15 浓度恢复到基础水平。在 2 年的随访中，HFF%的变化与 GDF15 的变化之间存在统计学显著关联（P=0.008；r=0.288）。
这些数据表明，超重/肥胖青少年的血浆 GDF15 浓度随肝内脂肪含量的变化而变化，可能作为儿童 NAFLD 的生物标志物。
