Combined metabolic activators therapy ameliorates liver fat in nonalcoholic fatty liver disease patients
Journal article, 2021
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.
multi-omics
systems biology
NAFLD
CMA
Author
Mujdat Zeybel
Nottingham University Hospitals NHS Trust
University of Nottingham
Koç University
Ozlem Altay
Royal Institute of Technology (KTH)
Muhammad Arif
Royal Institute of Technology (KTH)
Xiangyu Li
Royal Institute of Technology (KTH)
Hong Yang
Royal Institute of Technology (KTH)
Claudia Fredolini
Royal Institute of Technology (KTH)
Murat Akyildiz
Koç University
Burcin Saglam
Koç University
Mehmet Gokhan Gonenli
Koç University
Dilek Ural
Koç University
Woonghee Kim
Royal Institute of Technology (KTH)
J. M. Schwenk
Royal Institute of Technology (KTH)
C. Zhang
Royal Institute of Technology (KTH)
Zhengzhou University
Saeed Shoaie
Royal Institute of Technology (KTH)
King's College London
Jens B Nielsen
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
Mathias Uhlen
Royal Institute of Technology (KTH)
Jan Borén
University of Gothenburg
Adil Mardinoglu
Royal Institute of Technology (KTH)
King's College London
Molecular Systems Biology
17444292 (eISSN)
Vol. 17 10 e10459Subject Categories
Surgery
Other Clinical Medicine
Gastroenterology and Hepatology
DOI
10.15252/msb.202110459
PubMed
34694070