肝脂肪对减肥引起的血清肝细胞因子变化的贡献：一项随机对照试验。

Contribution of Liver Fat to Weight Loss-Induced Changes in Serum Hepatokines: A Randomized Controlled Trial.

机构信息

Department of Internal Medicine, Maastricht University Medical Center, Maastricht, Netherlands.

CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, Netherlands.

出版信息

J Clin Endocrinol Metab. 2019 Jul 1;104(7):2719-2727. doi: 10.1210/jc.2018-02378.

DOI:10.1210/jc.2018-02378

PMID:30753672

Abstract

CONTEXT

Hepatokines have emerged as potential mediators of obesity-associated comorbidities, such as type 2 diabetes, cardiovascular disease, fractures, and central hypogonadism.

OBJECTIVE

To assess whether weight loss-induced changes in hepatokines are mediated by intrahepatic triglyceride (IHTG) content.

DESIGN

Cross-sectional study and randomized controlled trial.

SETTING

General community.

PARTICIPANTS

Metabolically healthy, lean men (waist <94 cm; n = 25) and men with abdominal obesity (waist 102 to 110 cm; n = 52).

INTERVENTION

Men with abdominal obesity were randomized to 8-week dietary weight loss or no weight loss.

MAIN OUTCOME MEASURES

IHTG and serum hepatokines, that is, serum IGF1, IGF binding protein 1 (IGFBP1), SHBG, fibroblast growth factor 21 (FGF21), fetuin A, and plasma fetuin B.

RESULTS

All hepatokines, except for fetuin B, were significantly different between lean men and men with obesity. After the weight-loss intervention (-10.3 kg; 95% CI, -11.4 to-9.2), serum IGF1, IGFBP1, SHBG, and fetuin A approached the values observed in lean men. Cross-sectional associations were observed between IHTG and IGF1 (β = -0.51; 95% CI, -0.82 to -0.20), IGFBP1 (β = -4.2; 95% CI, -7.7 to -0.7), and FGF21 (β = 2.1; 95% CI, 1.3 to 2.9) in lean men and men with abdominal obesity combined. Weight loss resulted in a reduction of IHTG (treatment effect, -2.2%; 95% CI, -3.4% to -1.2%) that was associated with a change in IGF1 (β = -0.9; 95% CI, -1.3 to -0.4), IGFBP1 (β = -0.17; 95% CI, -0.31 to -0.03), and SHBG levels (β = -0.18; 95% CI, -0.29 to -0.07). Mediation analyses showed that only the weight loss-induced change in serum IGF1 was mediated by IHTG (mediated effect, 32.7%; 95% CI, 4.6% to 79.2%).

CONCLUSIONS

Dietary weight loss has differential effects on hepatokines. This study shows that the change in serum IGF1 levels after dietary weight loss is mediated by the change in IHTG content.

摘要

背景

肝脏激素已成为肥胖相关合并症（如 2 型糖尿病、心血管疾病、骨折和中枢性性腺功能减退症）的潜在介质。

目的

评估体重减轻引起的肝脏激素变化是否由肝内甘油三酯（IHTG）含量介导。

设计

横断面研究和随机对照试验。

地点

普通社区。

参与者

代谢健康、消瘦的男性（腰围<94cm；n=25）和腹部肥胖的男性（腰围 102 至 110cm；n=52）。

干预措施

腹部肥胖的男性被随机分为 8 周饮食减肥或不减肥。

主要观察指标

IHTG 和血清肝脏激素，即血清 IGF1、IGF 结合蛋白 1（IGFBP1）、SHBG、成纤维细胞生长因子 21（FGF21）、胎球蛋白 A 和血浆胎球蛋白 B。

结果

除胎球蛋白 B 外，所有肝脏激素在消瘦男性和肥胖男性之间均有显著差异。在减肥干预后（-10.3kg；95%CI，-11.4 至-9.2），血清 IGF1、IGFBP1、SHBG 和胎球蛋白 A 接近消瘦男性的水平。在消瘦男性和腹部肥胖男性中，IHTG 与 IGF1（β=-0.51；95%CI，-0.82 至-0.20）、IGFBP1（β=-4.2；95%CI，-7.7 至-0.7）和 FGF21（β=2.1；95%CI，1.3 至 2.9）之间存在横断面相关性。体重减轻导致 IHTG 减少（治疗效果，-2.2%；95%CI，-3.4%至-1.2%），这与 IGF1（β=-0.9；95%CI，-1.3 至-0.4）、IGFBP1（β=-0.17；95%CI，-0.31 至-0.03）和 SHBG 水平（β=-0.18；95%CI，-0.29 至-0.07）的变化相关。中介分析表明，只有饮食引起的血清 IGF1 变化是由 IHTG 介导的（中介效应，32.7%；95%CI，4.6%至 79.2%）。