通过成纤维细胞生长因子 19 上调肝胆汁酸合成在胆石病中是有缺陷的，但在超重个体中是有功能的。
Upregulation of hepatic bile acid synthesis via fibroblast growth factor 19 is defective in gallstone disease but functional in overweight individuals.
机构信息
Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology and University of Tuebingen, Stuttgart, Germany.
University Hospital Regensburg, Regensburg, Germany.
出版信息
United European Gastroenterol J. 2014 Jun;2(3):216-25. doi: 10.1177/2050640614527938.
BACKGROUND
Fibroblast growth factor 19 (FGF19) is an enteric hormone regulating bile acid de novo synthesis by sensing ileal bile acid flux. However, the role of FGF19 in cholelithiasis has not yet been elucidated and therefore is investigated in the present study.
METHODS
Total mRNA and protein were isolated from ileal biopsies and used for tissue expression analysis. FGF19, 7α-hydroxycholesterol (7α-OH-Chol), 27-hydroxycholesterol (27-OH-Chol), and different bile acids were determined in the blood samples.
RESULTS
FGF19 serum levels did not differ between gallstone carriers and controls but were significantly decreased in the overweight individuals (-32%, p = 0.0002), irrespective of gallstone status (normalweight to overweight controls -29%, p = 0.0017; normalweight to overweight gallstone carriers -44%, p = 0.0338), and correlated inversely with bodyweight (p < 0.0001, ρ = -0.3317). Compared to non-overweight controls, apical sodium-dependent bile acid transporter expression was significantly diminished in the non-overweight gallstone carriers (-42%, P mRNA = 0.0393; -52%, p protein = 0.0169) as well as in the overweight controls (-24%, P mRNA = 0.0148; -43%, p protein = 0.0017). FGF19 expression varied widely and was similar in all groups. A significant negative correlation was noted between 7α-OH-Chol, 27-OH-Chol, and FGF19 serum levels (p < 0.01; ρ7α-OH-Chol = -0.2155; ρ27-OH-Chol = -0.2144) in obesity.
CONCLUSION
Upregulation of hepatic bile acid synthesis via FGF 19 is defective in gallstone disease but functional in overweight individuals.
背景
成纤维细胞生长因子 19（FGF19）是一种肠激素，通过感应回肠胆汁酸流量来调节胆汁酸从头合成。然而，FGF19 在胆石症中的作用尚未阐明，因此本研究对此进行了探讨。
方法
从回肠活检组织中分离总 mRNA 和蛋白质，用于组织表达分析。检测血液样本中的 FGF19、7α-羟胆固醇（7α-OH-Chol）、27-羟胆固醇（27-OH-Chol）和不同的胆汁酸。
结果
胆石症患者与对照组的血清 FGF19 水平无差异，但超重者显著降低（-32%，p=0.0002），与胆石症状态无关（正常体重至超重对照组-29%，p=0.0017；正常体重至超重胆石症患者-44%，p=0.0338），且与体重呈负相关（p<0.0001，ρ=-0.3317）。与非超重对照组相比，非超重胆石症患者的顶侧钠依赖性胆汁酸转运蛋白表达显著降低（mRNA：-42%，P=0.0393；蛋白：-52%，p=0.0169），超重对照组也如此（mRNA：-24%，P=0.0148；蛋白：-43%，p=0.0017）。FGF19 表达差异很大，所有组之间相似。7α-OH-Chol、27-OH-Chol 和 FGF19 血清水平之间存在显著负相关（p<0.01；ρ7α-OH-Chol=-0.2155；ρ27-OH-Chol=-0.2144）。
结论
通过 FGF19 上调肝胆汁酸合成在胆石症中存在缺陷，但在超重者中功能正常。
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