Digestive physiology of the pig symposium: intestinal bile acid sensing is linked to key endocrine and metabolic signaling pathways.

Digestive physiology of the pig symposium: intestinal bile acid sensing is linked to key endocrine and metabolic signaling pathways.
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DOI:
10.2527/jas.2013-6331
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发表时间:
2013-05
影响因子:
3.3
通讯作者:
Moore D
Moore D
中科院分区:
农林科学2区
文献类型:
--
作者:
Burrin D;Stoll B;Moore D

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胆汁酸历来被认为主要在胆固醇稳态中起作用,并促进胃肠道中的脂肪消化。最近的发现表明,胆汁酸也作为信号分子发挥作用,通过激活G蛋白偶联胆汁酸受体1(GPBAR 1/G蛋白偶联胆汁酸受体1或TGR 5)(一种膜G蛋白偶联受体)和法尼醇×受体(FXR)(核激素受体超家族成员)发挥多种内分泌和代谢作用。这些胆汁酸敏感受体在肠上皮细胞中表达,TGR 5在肠内分泌细胞中表达,FXR在肠上皮细胞中表达,其排列在肠腔的粘膜中。胆汁酸激活肠道FXR的主要作用是分泌成纤维细胞生长因子(FGF)19,这是一种新型肠因子,可作为中枢肝肠信号维持肝脏中胆汁酸的稳态。肠内分泌细胞上TGR 5的激活刺激胰高血糖素样肽(GLP)-1和-2的分泌,其分别作为参与葡萄糖稳态的主要肠促胰岛素激素和响应于食物摄取的肠适应和生长中的关键营养激素起作用。胆汁酸激活肠道FXR和TGR 5所诱导的生物学作用对几种代谢性疾病(如胆汁淤积和糖尿病)的发病机制和治疗具有重要的治疗意义。本文综述了肠道胆汁酸传感和代谢功能生物学的这些新进展,并讨论了家猪健康和农业生产的潜在影响。
Bile acids have historically been considered to mainly function in cholesterol homeostasis and facilitate fat digestion in the gastrointestinal tract. Recent discoveries show that bile acids also function as signaling molecules that exert diverse endocrine and metabolic actions by activating G protein-coupled bile acid receptor 1 (GPBAR1/G-protein-coupled bile acid receptor 1 or TGR5), a membrane G protein-coupled receptor, and farnesoid × receptor (FXR), a member of the nuclear hormone receptor superfamily. These bile acid sensing receptors are expressed in intestinal epithelial cells, TGR5 in enteroendocrine cells and FXR in enterocytes, which line the mucosa of gut lumen. A dominant effect of intestinal FXR activation by bile acids is secretion of fibroblast growth factor (FGF) 19, a novel enterokine that functions as a central enterohepatic signal to maintain bile acid homeostasis in the liver. Activation of TGR5 on enteroendocrine cells stimulates secretion of glucagon-like peptides (GLP)-1 and -2, which function, respectively, as the major incretin hormone involved in glucose homeostasis and key trophic hormone in intestinal adaptation and growth in response to food ingestion. The biological actions induced by bile acid activation of intestinal FXR and TGR5 have important therapeutic implications for the pathogenesis and treatment of several metabolic diseases, such as cholestasis and diabetes. This review highlights these new developments in the biology of intestinal bile acid sensing and metabolic function and discusses the potential implications for the health and agricultural production of domestic swine.
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