The acute effect of metabolic cofactor supplementation: a potential therapeutic strategy against non-alcoholic fatty liver disease
Artikel i vetenskaplig tidskrift, 2020
The prevalence of non-alcoholic fatty liver disease (NAFLD) continues to increase dramatically, and there is no approved medication for its treatment. Recently, we predicted the underlying molecular mechanisms involved in the progression of NAFLD using network analysis and identified metabolic cofactors that might be beneficial as supplements to decrease human liver fat. Here, we first assessed the tolerability of the combined metabolic cofactors including l-serine, N-acetyl-l-cysteine (NAC), nicotinamide riboside (NR), and l-carnitine by performing a 7-day rat toxicology study. Second, we performed a human calibration study by supplementing combined metabolic cofactors and a control study to study the kinetics of these metabolites in the plasma of healthy subjects with and without supplementation. We measured clinical parameters and observed no immediate side effects. Next, we generated plasma metabolomics and inflammatory protein markers data to reveal the acute changes associated with the supplementation of the metabolic cofactors. We also integrated metabolomics data using personalized genome-scale metabolic modeling and observed that such supplementation significantly affects the global human lipid, amino acid, and antioxidant metabolism. Finally, we predicted blood concentrations of these compounds during daily long-term supplementation by generating an ordinary differential equation model and liver concentrations of serine by generating a pharmacokinetic model and finally adjusted the doses of individual metabolic cofactors for future human clinical trials.
and l-carnitine
nicotinamide riboside (NR)
NAFLD
N-acetyl-l-cysteine (NAC)
systems medicine
l-serine
Författare
C. Zhang
Zhengzhou University
Kungliga Tekniska Högskolan (KTH)
Elias Björnson
Göteborgs universitet
Chalmers, Biologi och bioteknik, Systembiologi
Muhammad Arif
Kungliga Tekniska Högskolan (KTH)
Abdellah Tebani
Kungliga Tekniska Högskolan (KTH)
Alen Lovric
Kungliga Tekniska Högskolan (KTH)
Karolinska universitetssjukhuset
Rui Benfeitas
Kungliga Tekniska Högskolan (KTH)
Stockholms universitet
Mehmet Ozcan
Kungliga Tekniska Högskolan (KTH)
Kajetan Juszczak
Kungliga Tekniska Högskolan (KTH)
Woonghee Kim
Kungliga Tekniska Högskolan (KTH)
Jung Tae Kim
Kungliga Tekniska Högskolan (KTH)
Gholamreza Bidkhori
King's College London
Marcus Stahlman
Göteborgs universitet
Per-Olof Bergh
Göteborgs universitet
Martin Adiels
Göteborgs universitet
Hasan Turkez
Atatürk Üniversitesi
Marja-Riitta Taskinen
Helsingin Yliopisto
Jim Bosley
Clermont Bosley LLC
Hanns-Ulrich Marschall
Göteborgs universitet
Jens B Nielsen
Chalmers, Biologi och bioteknik, Systembiologi
Mathias Uhlen
Kungliga Tekniska Högskolan (KTH)
Jan Boren
Göteborgs universitet
Adil Mardinoglu
King's College London
Kungliga Tekniska Högskolan (KTH)
Molecular Systems Biology
17444292 (eISSN)
Vol. 16 4 e9495Ämneskategorier
Farmaceutisk vetenskap
Annan klinisk medicin
Farmakologi och toxikologi
DOI
10.15252/msb.209495
PubMed
32337855