1. Combined metabolic activators therapy ameliorates liver fat in nonalcoholic fatty liver disease patients
- Author
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Woong-Hee Kim, Muhammad Arif, Ozlem Altay, Xiangyu Li, Hong Yang, Mujdat Zeybel, Claudia Fredolini, Mathias Uhlén, Jochen M. Schwenk, Jan Borén, Saeed Shoaie, Adil Mardinoglu, Jens Nielsen, Murat Akyildiz, Mehmet Gokhan Gonenli, Cheng Zhang, Dilek Ural, Burcin Saglam, Zeybel, Müjdat (ORCID 0000-0002-1542-117X & YÖK ID 214694), Ural, Dilek (ORCID 0000-0001-6419-0323 & YÖK ID 1057), Gönenli, Mehmet Gökhan (ORCID 0000-0003-2925-7048 & YÖK ID 350445), Akyıldız, Murat (ORCID 0000-0002-2080-7528 & YÖK ID 123080), Sağlam, Burçin, Altay, O., Arif, M., Li, X., Yang, H., Fredolini, C., Kim, W., Schwenk, J.M., Zhang, C., Shoaie, S., Nielsen, J., Uhlen, M., Boren, J., Mardinoğlu, A., Koç University Hospital, and School of Medicine
- Subjects
Medicine (General) ,medicine.medical_specialty ,QH301-705.5 ,Inflammation ,CMA ,Biology ,Mitochondrion ,medicine.disease_cause ,Diet, High-Fat ,Multi-omics ,NAFLD ,Systems biology ,General Biochemistry, Genetics and Molecular Biology ,Article ,chemistry.chemical_compound ,Mice ,R5-920 ,Weight loss ,Non-alcoholic Fatty Liver Disease ,Internal medicine ,Nonalcoholic fatty liver disease ,Weight Loss ,multi‐omics ,medicine ,Animals ,Humans ,Pharmacology & Drug Discovery ,Biology (General) ,Creatinine ,General Immunology and Microbiology ,Applied Mathematics ,systems biology ,Articles ,medicine.disease ,humanities ,Mice, Inbred C57BL ,Endocrinology ,Metabolism ,Computational Theory and Mathematics ,chemistry ,Liver ,Biochemistry and molecular biology ,Uric acid ,Steatosis ,medicine.symptom ,General Agricultural and Biological Sciences ,Oxidative stress ,Information Systems - Abstract
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 (CMAs) 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 metagenomic 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 showed that CMA can be used to develop a pharmacological treatment strategy in NAFLD patients., A placebo‐controlled human study shows that oral administration of Combined Metabolic Activators (CMA) reduces liver fat in nonalcoholic fatty liver disease (NAFLD) patients.
- Published
- 2021