* If you want to update the article please login/register
Here, we outlined a novel way by which OCA improves NAFLD by stimulating hepatic long-chain fatty acids uptake. OCA inhibited hFATP5 more than murine FATP5 as determined by LCFAs uptake in FATP5 representing HEK-293. In primary hepatocytes from hFATP5 mice, FXR-/-/hFATP5 mice, more than in mice ex vivo, but ex vivo. In addition, OCA reduced LCFAs uptake by livers in hFATP5 mice and FXR-/-/hFATP5 mice, but not in FXR-/- mice in vivo. For hFATP5 mice and FXR-/-/5 mice, respectively, 63% and 53% were reduced, but not in FXR-/- mice. This means that the therapeutic effects of OCA on NAFLD in vivo are mediated by a specific, hFATP5-dependent mechanism.
Source link: https://doi.org/10.1016/j.biopha.2022.112984
However, new clinical studies showed that OCA might not be safe against liver fibrosis, perhaps due to the lower dosage to minimize the risk of the side-effect of pruritus. For those combating liver fibrosis, we recommend a combinatory therapeutic approach of OCA and apoptosis inhibitors. According to our report, OCA partially inhibits HSC release/proliferation by banning BA homeostasis and, thus stopping HSC activation. The results of this research indicate that a combination of apoptosis inhibitor and OCA at a lower dosage may be a new therapeutic approach for liver fibrosis.
Source link: https://doi.org/10.1016/j.apsb.2018.11.004
Male C57BL/6 mice were fed either a standard-chow diet or a high-fat diet in NAFLD. The aim of this research was to determine the role of farnesoid X receptor agonist obeticholic acid in NAFLD. Obetiholic acid therapy has been shown to have a significant effect on liver inflammation, the intestinal barrier, endotoxemia, gut microbiome, and intestinal barrier damage caused by HFD.
During 17-ethylestradiol-induced gestational cholestasis in mice, we investigated the effects of obeticholic acid on fetal intrauterine growth restriction. From gestational day 13 to GD17, all pregnant mice except controls were subcutaneously injected with E2 daily. From GD12 to GD17, some pregnant mice were orally administered with OCA daily. In addition, late pregnancy exposure with E2 triggered cholestasis, which OCA prevented E2-induced cholestasis. During cholestasis, OCA reduced the risk of IUGR during cholestasis. Interestingly, OCA slowed the erosion of blood sinusoid area in the placental labyrinth layer and stifled downregulation of placental sodium-coupled nucle acid transporter- 2 during cholestasis. During cholestasis, OCA reduced glutathione depletion and lipid peroxidation in placenta and fetal liver liver, and placental protein nitration during cholestasis, according to a new study. During cholestasis, OCA activated antioxidant Nrf2 signaling. Overall, we found that OCA treatment improved gestational cholestasis-induced placental dysfunction and IUGR by minimizing placental oxidative stress and retaining bile acid homeostasis.
Source link: https://doi.org/10.1155/2019/7419249
* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions