Li G, Yin J, Fu J, Li L, Grant S F A, Li C, Li M, Mi J, Li M, Gao S
Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing 100730, China.
Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing 100730, China; Department of Endocrinology, First Affiliated Hospital, Shanxi Medical University, Shanxi 030001, China.
Diabetes Metab. 2017 Jun;43(3):253-260. doi: 10.1016/j.diabet.2016.12.003. Epub 2017 Jan 27.
Fibroblast growth factor 21 (FGF21) exerts beneficial effects on metabolic homoeostasis and has been reported to be regulated by adiponectin, leptin and resistin. However, while an association between increased circulating FGF21 and metabolic disorders has been reported in adults, paediatric-specific data are lacking.
This study investigated the relationship between FGF21 levels and obesity, insulin resistance (IR), the metabolic syndrome (MetS) and adipokines (adiponectin, leptin and resistin) in a cohort of 3231 Chinese youngsters aged 6-18.
There were gender- and puberty-related differences in FGF21 levels. Unexpectedly, FGF21 levels were decreased in children with obesity, and negatively correlated with insulin, HOMA-IR and leptin levels after adjusting for age, gender, puberty and lifestyle factors. Moreover, multiple regression analyses showed that serum FGF21 positively predicted adiponectin levels while resistin positively predicted FGF21 levels independent of BMI (P<0.05). Children in the lowest FGF21 quintile were more likely to have IR (OR: 1.85, 95% CI: 1.41-2.42; P=0.002) and MetS (OR: 1.62, 95% CI: 1.14-2.28; P=0.007) than those in the highest quintile. Further adjusting for BMI and/or the three adipokines modified the association of FGF21 with MetS (P>0.10) but not with IR (P<0.01).
Although the associations between adiponectin, leptin, resistin and metabolic abnormalities in our paediatric population were similar to those in adults, correlations of FGF21 levels with obesity, IR and MetS were the inverse of those found in adults. Our present findings suggest that FGF21 deficiency, rather than resistance, contribute to IR and hypoadiponectinaemia independently of obesity in young people.
成纤维细胞生长因子21(FGF21)对代谢稳态具有有益作用,据报道其受脂联素、瘦素和抵抗素调节。然而,虽然在成年人中已报道循环FGF21升高与代谢紊乱之间存在关联,但缺乏儿科特异性数据。
本研究调查了3231名6至18岁中国青少年队列中FGF21水平与肥胖、胰岛素抵抗(IR)、代谢综合征(MetS)和脂肪因子(脂联素、瘦素和抵抗素)之间的关系。
FGF21水平存在性别和青春期相关差异。出乎意料的是,肥胖儿童的FGF21水平降低,在调整年龄、性别、青春期和生活方式因素后,其与胰岛素、HOMA-IR和瘦素水平呈负相关。此外,多元回归分析表明,血清FGF21正向预测脂联素水平,而抵抗素正向预测FGF21水平,且独立于BMI(P<0.05)。FGF21五分位数最低的儿童比最高五分位数的儿童更有可能患有IR(OR:1.85,95%CI:1.41-2.42;P=0.002)和MetS(OR:1.62,95%CI:1.14-2.28;P=0.007)。进一步调整BMI和/或三种脂肪因子后,改变了FGF21与MetS的关联(P>0.10),但未改变其与IR的关联(P<0.01)。
虽然我们儿科人群中脂联素、瘦素、抵抗素与代谢异常之间的关联与成年人相似,但FGF21水平与肥胖、IR和MetS的相关性与成年人相反。我们目前的研究结果表明,FGF21缺乏而非抵抗,在年轻人中独立于肥胖导致IR和低脂联素血症。