The acute effect of metabolic cofactor supplementation: a potential therapeutic strategy against non-alc33oholic 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.

nicotinamide riboside (NR)

and l-carnitine

N-acetyl-l-cysteine (NAC)

NAFLD

systems medicine

l-serine

Författare

C. Zhang

Zhengzhou University

Kungliga Tekniska Högskolan (KTH)

Elias Bjornson

Göteborgs universitet

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

1744-4292 (ISSN)

Vol. 16 4 e9495

Ämneskategorier

Farmaceutisk vetenskap

Annan klinisk medicin

Farmakologi och toxikologi

DOI

10.15252/msb.209495

PubMed

32337855

Mer information

Senast uppdaterat

2020-09-04