Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Yufu City, Oita, Japan.
Department of Gastroenterology, Faculty of Medicine, Oita University, Oita, Japan.
Sci Rep. 2020 Oct 30;10(1):18768. doi: 10.1038/s41598-020-75542-3.
Non-alcoholic fatty liver disease (NAFLD) is a significant problem because its prevalence is increasing worldwide. Recent animal studies have identified gut microbiota as a potentially important player in the pathogenesis of NAFLD. Previously, we reported that the administration of branched-chain amino acids (BCAAs) reduces hepatic fat accumulation in experimental animal models. This study aimed to clarify how changes in the intestinal microbial flora following the administration of BCAAs affect a high-fat diet (HF)-induced fat accumulation in the liver. We examined whether the administration of BCAAs alters the development of hepatic fat accumulation as well as intestinal microbial flora. The oral administration of BCAAs (3% kcal) induced a significant increase in Ruminococcus flavefaciens (R. flavefaciens) and portal acetic acid levels, and it reduced hepatic fat accumulation in HF-fed rats. In addition, BCAAs reduced the expression of the lipogenesis-related genes FAS and ACC in the liver. Furthermore, we observed that R. flavefaciens is essential for promoting a BCAA-induced reduction in hepatic fat accumulation. These data suggest that BCAA treatment induces the proliferation of intestinal flora including R. flavefaciens and that portal acetic acid synthesized from intestinal flora improves NAFLD by downregulating the expression of FAS and ACC in the liver.
非酒精性脂肪性肝病（NAFLD）是一个重大问题，因为其在全球范围内的患病率正在增加。最近的动物研究已经确定肠道微生物群是 NAFLD 发病机制中的一个潜在重要因素。此前，我们报告称，支链氨基酸（BCAAs）的给药可减少实验动物模型中的肝脂肪堆积。本研究旨在阐明 BCAAs 给药后肠道微生物菌群的变化如何影响高脂肪饮食（HF）诱导的肝脏脂肪堆积。我们检查了 BCAAs 的给药是否改变了肝脂肪堆积的发展以及肠道微生物菌群。BCAAs（3%卡路里）的口服给药可显著增加瘤胃球菌（R. flavefaciens）和门脉乙酸水平，并减少 HF 喂养大鼠的肝脂肪堆积。此外，BCAAs 降低了肝脏中与脂肪生成相关的基因 FAS 和 ACC 的表达。此外，我们观察到 R. flavefaciens 对于促进 BCAA 诱导的肝脂肪减少是必需的。这些数据表明，BCAA 治疗诱导包括 R. flavefaciens 在内的肠道菌群的增殖，并且来自肠道菌群的门脉乙酸通过下调肝脏中 FAS 和 ACC 的表达来改善 NAFLD。
