Yao Zheng, Guo Jia, Du Bing, Hong Li, Zhu Ying, Feng Xiaoyi, Hou Yuanlu, Shi Anhua
School of Basic Medical Sciences, Yunnan University of Chinese Medicine, Kunming, China.
The Key Laboratory of Microcosmic Syndrome Differentiation, Education Department of Yunnan, Yunnan University of Chinese Medicine, Kunming, China.
Front Microbiol. 2023 Jul 18;14:1147067. doi: 10.3389/fmicb.2023.1147067. eCollection 2023.
BACKGROUND & PURPOSE: Non-alcoholic fatty liver disease (NAFLD) is characterised by the excessive accumulation of triglycerides in the liver. Shenling Baizhu powder (SLBZP) is formulated from various natural medicinal plants that protect the liver and are used to treat intestinal diseases. SLBZP improves the symptoms of NAFLD. However, its mechanism of action remains unclear. Herein, we investigated the ameliorative effect of SLBZP on model mice with high-fat-diet (HFD)-induced NAFLD. Additionally, we evaluated the impact of SLBZP on the intestinal flora and its metabolites and mitochondrial energy metabolism in NAFLD.
We used HFD to establish a mouse model of NAFLD. Different drug interventions were administered. We measured serum biochemical indices. Liver sections were visualised with hematoxylin-eosin and oil red O staining. amplicon sequencing technology was used to analyse the diversity and abundance of the intestinal flora. Short-chain fatty acids (SCFAs) in the intestinal contents were detected using GC-MS. Liver tissue was sampled to detect mitochondrial membrane functional indices. Western blotting was used to determine the levels of mitochondrial pathway-related proteins, namely, uncoupling protein 2 (UCP2), adenosine monophosphate-activated protein kinase (AMPK) and inhibitory factor 1 (IF1) of F1Fo ATP synthesis/hydrolase, in the liver.
The spleen-invigorating classic recipe of SLBZP reduced liver lipid deposition in mice with HFD-induced NAFLD. Additionally, SCFAs produced by intestinal flora metabolism regulated the UCP2/AMPK/IF1 signalling pathway involved in liver mitochondrial energy metabolism to improve the liver mitochondrial membrane permeability, respiratory state and oxidative phosphorylation efficiency of mice with NAFLD. Finally, SLBZP increased the liver ATP level.
Our results suggest that the therapeutic effect of SLBZP on NAFLD is related to the regulation of hepatic mitochondrial energy metabolism by intestinal flora and its metabolites and is possibly associated with the UCP2/AMPK/IF1 signalling pathway.
非酒精性脂肪性肝病（NAFLD）的特征是肝脏中甘油三酯过度蓄积。参苓白术散（SLBZP）由多种保肝且用于治疗肠道疾病的天然药用植物制成。SLBZP可改善NAFLD的症状。然而，其作用机制尚不清楚。在此，我们研究了SLBZP对高脂饮食（HFD）诱导的NAFLD模型小鼠的改善作用。此外，我们评估了SLBZP对NAFLD小鼠肠道菌群及其代谢产物以及线粒体能量代谢的影响。
我们用HFD建立NAFLD小鼠模型。给予不同的药物干预。我们检测血清生化指标。用苏木精-伊红和油红O染色观察肝组织切片。采用扩增子测序技术分析肠道菌群的多样性和丰度。用气相色谱-质谱联用仪检测肠内容物中的短链脂肪酸（SCFAs）。采集肝组织样本检测线粒体膜功能指标。用蛋白质免疫印迹法测定肝脏中线粒体途径相关蛋白的水平，即解偶联蛋白2（UCP2）、腺苷酸活化蛋白激酶（AMPK）和F1Fo ATP合成/水解酶的抑制因子1（IF1）。
SLBZP这一健脾经典方剂减少了HFD诱导的NAFLD小鼠的肝脏脂质沉积。此外，肠道菌群代谢产生的SCFAs调节参与肝脏线粒体能量代谢的UCP2/AMPK/IF1信号通路，以改善NAFLD小鼠的肝脏线粒体膜通透性、呼吸状态和氧化磷酸化效率。最后，SLBZP提高了肝脏ATP水平。
我们的结果表明，SLBZP对NAFLD的治疗作用与肠道菌群及其代谢产物对肝脏线粒体能量代谢的调节有关，可能与UCP2/AMPK/IF1信号通路有关。
