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首页> 外文期刊>Current opinion in lipidology >Regulation of bile acid homeostasis by the intestinal Diet1-FGF15/19 axis
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Regulation of bile acid homeostasis by the intestinal Diet1-FGF15/19 axis

机译:肠道Diet1-FGF15 / 19轴对胆汁酸稳态的调节

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PURPOSE OF REVIEW: Hepatic bile acid synthesis is controlled, in part, by a complex enterohepatic feedback regulatory mechanism. In this review, we focus on the role of the intestinal FGF15/19 hormone in modulating bile acid levels, and additional metabolic effects on glucose metabolism, nonalcoholic liver disease (NAFLD), and liver regeneration. We also highlight the newly identified intestinal protein, Diet1, which is a modulator of FGF15/19 levels. RECENT FINDINGS: Low FGF19 levels are associated with bile acid diarrhea and NAFLD. In contrast, high FGF19 levels are associated with diabetes remission following Roux-en-Y gastric bypass surgery, suggesting new therapeutic approaches against type 2 diabetes. The effect of FGF15/19 on liver plasticity is a double-edged sword: whereas elevated FGF15/19 levels improve survival of mice after partial hepatectomy, FGF19 mitogenic activity is associated with liver carcinoma. Finally, a recent study has identified Diet1, an intestinal factor that influences FGF15/19 levels in mouse intestine and human enterocytes. Diet1 represents the first factor shown to influence FGF15/19 levels at a post-transcriptional level. SUMMARY: The biological effects of FGF15/19 make it an attractive target for treating metabolic dysregulation underlying conditions such as fatty liver and type 2 diabetes. Further elucidation of the role of Diet1 in FGF15/19 secretion may provide a control point for the pharmacological modulation of FGF15/19 levels.
机译:审查目的:肝胆汁酸的合成部分受复杂的肝肝反馈调节机制控制。在这篇综述中,我们集中于肠道FGF15 / 19激素在调节胆汁酸水平中的作用,以及对葡萄糖代谢,非酒精性肝病(NAFLD)和肝脏再生的其他代谢作用。我们还重点介绍了新发现的肠道蛋白质Diet1,它是FGF15 / 19水平的调节剂。最近的发现:FGF19水平低与胆汁酸腹泻和NAFLD有关。相比之下,Roux-en-Y胃搭桥手术后高FGF19水平与糖尿病缓解相关,这表明针对2型糖尿病的新治疗方法。 FGF15 / 19对肝脏可塑性的影响是一把双刃剑:尽管FGF15 / 19水平升高可提高部分肝切除术后小鼠的存活率,但FGF19有丝分裂活性与肝癌有关。最后,最近的一项研究确定了Diet1,这是一种影响小鼠肠和人肠上皮细胞中FGF15 / 19水平的肠因子。 Diet1代表在转录后水平上影响FGF15 / 19水平的第一个因素。简介:FGF15 / 19的生物学效应使其成为治疗潜在疾病如脂肪肝和2型糖尿病的代谢异常的诱人靶标。 Diet1在FGF15 / 19分泌中的作用的进一步阐明可能为FGF15 / 19水平的药理调节提供控制点。

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