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成纤维细胞生长因子 19:治疗非酒精性脂肪性肝病的肝脏代谢潜在调节剂。

Fibroblast Growth Factor 19: Potential modulation of hepatic metabolism for the treatment of non-alcoholic fatty liver disease.

机构信息

Department of Nutritional Sciences, Oklahoma State University, Stillwater, OK, USA.

Department of Pediatric Gastroenterology and Hepatology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.

出版信息

Liver Int. 2021 May;41(5):894-904. doi: 10.1111/liv.14802. Epub 2021 Feb 13.

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a spectrum of liver disease that is becoming more prevalent in concert with obesity and poor lifestyle habits. Although NAFLD is treatable via lifestyle modification in early stages, more advanced liver pathologies (eg non-alcoholic steatohepatitis [NASH]) are harder to reverse. There is no Food and Drug Administration approved pharmacological treatment for NAFLD, and little research has been done to identify compounds that target key NAFLD mechanisms. Bile acids and bile acid receptors have been implicated in NAFLD pathogenesis and modulating bile acids and bile acid receptors has recently been targeted as a therapeutic treatment option for NAFLD. Fibroblast growth factor 19 (FGF19), a nutritionally regulated post-prandial hormone, is a chief regulator of bile acid metabolism and an important player in lipid and carbohydrate metabolism, including key mechanisms of NAFLD pathogenesis. In this review, we discuss recent findings related to FGF19-regulated processes involved in the pathogenesis of NAFLD. We summarize known and conjectural frameworks and limitations for the clinical application of FGF19-targeted therapies as they relate to NAFLD.

摘要

非酒精性脂肪性肝病(NAFLD)是一种与肥胖和不良生活习惯相关的肝脏疾病谱,其发病率正在上升。虽然在疾病早期通过生活方式改变可以治疗 NAFLD,但更严重的肝脏病变(如非酒精性脂肪性肝炎[NASH])则更难逆转。目前尚无美国食品和药物管理局批准的治疗 NAFLD 的药物,并且很少有研究用于确定针对 NAFLD 关键机制的化合物。胆汁酸和胆汁酸受体与 NAFLD 的发病机制有关,最近已将调节胆汁酸和胆汁酸受体作为治疗 NAFLD 的一种治疗选择。成纤维细胞生长因子 19(FGF19)是一种营养调节的餐后激素,是胆汁酸代谢的主要调节剂,也是脂质和碳水化合物代谢的重要参与者,包括 NAFLD 发病机制的关键机制。在这篇综述中,我们讨论了与 FGF19 调节的 NAFLD 发病机制相关的最新发现。我们总结了已知的和推测的框架以及 FGF19 靶向治疗在临床应用中的局限性,因为它们与 NAFLD 有关。

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