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

1744-4292 (ISSN)

Vol. 17 10 e10459

Subject Categories

Surgery

Other Clinical Medicine

Gastroenterology and Hepatology

DOI

10.15252/msb.202110459

PubMed

34694070

More information

Latest update

11/11/2021