Combined metabolic activators therapy ameliorates liver fat in nonalcoholic fatty liver disease patients
Artikel i vetenskaplig tidskrift, 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
Författare
Mujdat Zeybel
Nottingham University Hospitals NHS Trust
University of Nottingham
Koç Üniversitesi
Ozlem Altay
Kungliga Tekniska Högskolan (KTH)
Muhammad Arif
Kungliga Tekniska Högskolan (KTH)
Xiangyu Li
Kungliga Tekniska Högskolan (KTH)
Hong Yang
Kungliga Tekniska Högskolan (KTH)
Claudia Fredolini
Kungliga Tekniska Högskolan (KTH)
Murat Akyildiz
Koç Üniversitesi
Burcin Saglam
Koç Üniversitesi
Mehmet Gokhan Gonenli
Koç Üniversitesi
Dilek Ural
Koç Üniversitesi
Woonghee Kim
Kungliga Tekniska Högskolan (KTH)
J. M. Schwenk
Kungliga Tekniska Högskolan (KTH)
C. Zhang
Kungliga Tekniska Högskolan (KTH)
Zhengzhou University
Saeed Shoaie
Kungliga Tekniska Högskolan (KTH)
King's College London
Jens B Nielsen
Chalmers, Biologi och bioteknik, Systembiologi
Mathias Uhlen
Kungliga Tekniska Högskolan (KTH)
Jan Borén
Göteborgs universitet
Adil Mardinoglu
Kungliga Tekniska Högskolan (KTH)
King's College London
Molecular Systems Biology
17444292 (eISSN)
Vol. 17 10 e10459Ämneskategorier
Kirurgi
Annan klinisk medicin
Gastroenterologi
DOI
10.15252/msb.202110459
PubMed
34694070