Johansson Helene, Mörk Lisa-Mari, Li Meng, Sandblom Anita L, Björkhem Ingemar, Höijer Jonas, Ericzon Bo-Göran, Jorns Carl, Gilg Stefan, Sparrelid Ernesto, Isaksson Bengt, Nowak Greg, Ellis Ewa
Division of Transplantation Surgery, Karolinska Institutet and Karolinska University Hospital Huddinge, Stockholm, Sweden.
Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet and Karolinska University Hospital Huddinge, Stockholm, Sweden.
J Clin Exp Hepatol. 2018 Jun;8(2):162-168. doi: 10.1016/j.jceh.2017.07.001. Epub 2017 Jul 28.
Bile acid homeostasis is essential and imbalance may lead to liver damage and liver failure. The bile acid induced intestinal factor fibroblast growth factor 19 (FGF19) has been identified as a key protein for mediating negative feedback inhibition of bile acid synthesis. The aim of the study was to define FGF19 and bile acid concentrations in portal and systemic blood in the fasted and postprandial state. We also addressed the question if physiological portal levels of FGF19 can be extrapolated from the concentration in systemic blood.
Portal and systemic blood was collected from 75 fasted patients undergoing liver surgery and from three organ donors before and after enteral nutrition. Serum concentration of FGF19 was determined with ELISA and bile acid concentration with gas chromatography-mass spectrometry.
Concentration of bile acids was twice as high in portal compared to systemic blood in the fasted group and 3-5 times higher in the postprandial group. FGF19 increased after enteral nutrition but did not differ between portal and systemic blood, in either group. In addition, a strong, positive correlation between bile acids and FGF19 was found.
Our results confirm that bile acids drive the postprandial increase of circulating FGF19 but a hepatic clearance of FGF19 is unlikely. We conclude that systemic concentrations of FGF19 reflect portal concentrations of FGF19.
胆汁酸稳态至关重要，失衡可能导致肝损伤和肝衰竭。胆汁酸诱导的肠道因子成纤维细胞生长因子19（FGF19）已被确定为介导胆汁酸合成负反馈抑制的关键蛋白。本研究的目的是确定空腹和餐后状态下门静脉血和全身血中FGF19和胆汁酸的浓度。我们还探讨了能否从全身血浓度推断FGF19的生理门静脉水平这一问题。
收集75例接受肝脏手术的空腹患者以及3例器官捐献者在肠内营养前后的门静脉血和全身血。采用酶联免疫吸附测定法测定FGF19的血清浓度，采用气相色谱 - 质谱法测定胆汁酸浓度。
空腹组门静脉中胆汁酸浓度是全身血中的两倍，餐后组则高出3 - 5倍。肠内营养后FGF19升高，但两组门静脉血和全身血中的FGF19浓度均无差异。此外，发现胆汁酸与FGF19之间存在强正相关。
我们的结果证实胆汁酸驱动餐后循环中FGF19的增加，但FGF19经肝脏清除的可能性不大。我们得出结论，FGF19的全身浓度反映了FGF19的门静脉浓度。
