Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; Institute of Molecular biology & Bio-technology, Bahauddin Zakariya University, Multan, Pakistan.
Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Biochim Biophys Acta Mol Cell Biol Lipids. 2017 May;1862(5):496-512. doi: 10.1016/j.bbalip.2017.01.007. Epub 2017 Jan 19.
Vitamin A is a fat-soluble vitamin important for vision, reproduction, embryonic development, cell differentiation, epithelial barrier function and adequate immune responses. Efficient absorption of dietary vitamin A depends on the fat-solubilizing properties of bile acids. Bile acids are synthesized in the liver and maintained in an enterohepatic circulation. The liver is also the main storage site for vitamin A in the mammalian body, where an intimate collaboration between hepatocytes and hepatic stellate cells leads to the accumulation of retinyl esters in large cytoplasmic lipid droplet hepatic stellate cells. Chronic liver diseases are often characterized by disturbed bile acid and vitamin A homeostasis, where bile production is impaired and hepatic stellate cells lose their vitamin A in a transdifferentiation process to myofibroblasts, cells that produce excessive extracellular matrix proteins leading to fibrosis. Chronic liver diseases thus may lead to vitamin A deficiency. Recent data reveal an intricate crosstalk between vitamin A metabolites and bile acids, in part via the Retinoic Acid Receptor (RAR), Retinoid X Receptor (RXR) and the Farnesoid X Receptor (FXR), in maintaining vitamin A and bile acid homeostasis. Here, we provide an overview of the various levels of "communication" between vitamin A metabolites and bile acids and its relevance for the treatment of chronic liver diseases.
维生素 A 是一种脂溶性维生素，对视力、生殖、胚胎发育、细胞分化、上皮屏障功能和适当的免疫反应至关重要。膳食维生素 A 的有效吸收依赖于胆汁酸的脂溶性。胆汁酸在肝脏中合成，并在肠肝循环中维持。肝脏也是哺乳动物体内维生素 A 的主要储存部位，肝细胞和肝星状细胞之间的密切合作导致视黄酯在大的细胞质脂质滴中积累肝星状细胞。慢性肝病的特点通常是胆汁酸和维生素 A 稳态紊乱，胆汁生成受损，肝星状细胞在向肌成纤维细胞的转化过程中失去维生素 A，肌成纤维细胞产生过多的细胞外基质蛋白，导致纤维化。因此，慢性肝病可能导致维生素 A 缺乏。最近的数据揭示了维生素 A 代谢物和胆汁酸之间错综复杂的相互作用，部分通过视黄酸受体 (RAR)、类视黄醇 X 受体 (RXR) 和法尼醇 X 受体 (FXR)，在维持维生素 A 和胆汁酸稳态方面发挥作用。在这里，我们概述了维生素 A 代谢物和胆汁酸之间的各种“通讯”水平及其在慢性肝病治疗中的相关性。
