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Combined Metabolic Activators Reduces Liver Fat in Nonalcoholic Fatty Liver Disease Patients
medRxiv - Endocrinology Pub Date : 2021-05-23 , DOI: 10.1101/2021.05.20.21257480
Mujdat Zeybel , Ozlem Altay , Muhammad Arif , Xiangyu Li , Hong Yang , Claudia Fredolini , Murat Akyildiz , Burcin Saglam , Mehmet Gokhan Gonenli , Dilek Ural , Woonghee Kim , Jochen M. Schwenk , Cheng Zhang , Saeed Shoaie , Jens Nielsen , Mathias Uhlén , Jan Borén , Adil Mardinoglu

Nonalcoholic fatty liver disease (NAFLD) refers to excess fat accumulation in the liver. In animal experiments and human kinetic study, we found that administration of combined metabolic activators (CMA) promotes the oxidation of fat, attenuates the resulting oxidative stress, activates mitochondria and eventually removes excess fat from the liver. Here, we tested the safety and efficacy of CMA in NAFLD patients in a placebo-controlled 10-week study. We found that CMA significantly decreased hepatic steatosis and levels of aspartate aminotransferase, alanine aminotransferase, uric acid, and creatinine, whereas found no differences on these variables in the placebo group after adjustment for weight loss. By integrating clinical data with plasma metabolomics and inflammatory proteomics as well as oral and gut metagenomics data, we revealed the underlying molecular mechanisms associated with the reduced hepatic fat and inflammation in NAFLD patients and identified the key players involved in the host-microbiome interactions. In conclusion, we observed that CMA can be used develop a pharmacological treatment strategy in NAFLD patients.

中文翻译:

组合代谢活化剂可降低非酒精性脂肪肝病患者的肝脏脂肪

非酒精性脂肪肝疾病(NAFLD)是指肝脏中多余的脂肪积聚。在动物实验和人体动力学研究中,我们发现联合代谢激活剂(CMA)的使用可促进脂肪的氧化,减弱所产生的氧化应激,激活线粒体并最终从肝脏中去除多余的脂肪。在这里,我们在安慰剂对照的10周研究中测试了CMA在NAFLD患者中的安全性和有效性。我们发现,CMA显着降低了肝脂肪变性和天冬氨酸转氨酶,丙氨酸转氨酶,尿酸和肌酐的水平,而调整体重减轻后,安慰剂组在这些变量上没有差异。通过将临床数据与血浆代谢组学和炎性蛋白质组学以及口腔和肠道宏基因组学数据整合在一起,我们揭示了与NAFLD患者肝脂肪减少和炎症减少相关的潜在分子机制,并确定了参与宿主-微生物组相互作用的关键因素。总之,我们观察到CMA可用于开发NAFLD患者的药理治疗策略。
更新日期:2021-05-23
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