Styer Amanda M, Roesch Stephen L, Argyropoulos George
Weis Center for Research, Geisinger Health System, Danville, Pennsylvania, United States of America.
Weis Center for Research, Geisinger Health System, Danville, Pennsylvania, United States of America ; Institute of Obesity, Geisinger Health System, Danville, Pennsylvania, United States of America.
PLoS One. 2014 Jan 20;9(1):e85558. doi: 10.1371/journal.pone.0085558. eCollection 2014.
The enterohepatic pathway involving the fibroblast growth factor 19 (FGF19) and bile acids (BA) has been linked with the etiology and remission of type 2 diabetes (T2D) following Roux-en-Y gastric bypass (RYGB) surgery. Specifically, diabetic patients had lower FGF19 circulating levels but postoperative FGF19 and BA levels were higher in diabetic patients that experience remission of T2D, as compared to non-diabetic patients and diabetic patients that do not experience remission. It has been proposed that this may be due to the direct flow of digestate-free bile acids into the ileum benefiting mostly T2D patients without severe diabetes.
METHODS/RESULTS: We used a human colorectal cell line (LS174T) that endogenously expresses FGF19, real time PCR, and Elisas for precise quantitation of FGF19 mRNA and secreted protein levels. We report here that BA and fractions of BA stimulated FGF19 in vitro but this effect was partially blocked when BA were pre-incubated with a lipoprotein mix which emulates digested food. In addition, we show that FGF19 mRNA was stimulated by meal replacement drinks (Ensure, Glucerna, SlimFast), non-fat milk, and coffee which has been linked with reduced risk for developing diabetes. Pure caffeine and the 5-hour Energy drink, on the other hand, decreased FGF19 mRNA.
In summary, FGF19 expression in vitro is modifiable by popular drinks suggesting that such approaches could potentially be used for modulating FGF19 expression in humans.
涉及成纤维细胞生长因子19（FGF19）和胆汁酸（BA）的肠肝循环途径与Roux-en-Y胃旁路术（RYGB）后2型糖尿病（T2D）的病因及缓解相关。具体而言，糖尿病患者的FGF19循环水平较低，但与非糖尿病患者及未缓解的糖尿病患者相比，T2D缓解的糖尿病患者术后FGF19和BA水平更高。有人提出，这可能是由于不含消化物的胆汁酸直接流入回肠，主要使病情不严重的T2D患者受益。
方法/结果：我们使用了内源性表达FGF19的人结肠癌细胞系（LS174T）、实时定量PCR以及酶联免疫吸附测定法来精确量化FGF19 mRNA和分泌蛋白水平。我们在此报告，BA及其部分成分在体外可刺激FGF19，但当BA与模拟消化食物的脂蛋白混合物预孵育时，这种效应会被部分阻断。此外，我们发现代餐饮料（安素、益力佳、速纤）、脱脂牛奶和与降低糖尿病发病风险相关的咖啡可刺激FGF19 mRNA。另一方面，纯咖啡因和5小时能量饮料会降低FGF19 mRNA。
总之，体外FGF19的表达可被常见饮品改变，这表明此类方法可能可用于调节人体FGF19的表达。
