Longitudinal metabolomics analysis reveals the acute effect of cysteine and NAC included in the combined metabolic activators
Artikel i vetenskaplig tidskrift, 2023

Growing evidence suggests that the depletion of plasma NAD+ and glutathione (GSH) may play an important role in the development of metabolic disorders. The administration of Combined Metabolic Activators (CMA), consisting of GSH and NAD+ precursors, has been explored as a promising therapeutic strategy to target multiple altered pathways associated with the pathogenesis of the diseases. Although studies have examined the therapeutic effect of CMA that contains N-acetyl-L-cysteine (NAC) as a metabolic activator, a system-wide comparison of the metabolic response to the administration of CMA with NAC and cysteine remains lacking. In this placebo-controlled study, we studied the acute effect of the CMA administration with different metabolic activators, including NAC or cysteine with/without nicotinamide or flush free niacin, and performed longitudinal untargeted-metabolomics profiling of plasma obtained from 70 well-characterized healthy volunteers. The time-series metabolomics data revealed the metabolic pathways affected after the administration of CMAs showed high similarity between CMA containing nicotinamide and NAC or cysteine as metabolic activators. Our analysis also showed that CMA with cysteine is well-tolerated and safe in healthy individuals throughout the study. Last, our study systematically provided insights into a complex and dynamics landscape involved in amino acid, lipid and nicotinamide metabolism, reflecting the metabolic responses to CMA administration containing different metabolic activators.

Metabolomics

Nicotinamide

Combined metabolic activators

Niacin

N-Acetyl-L-cysteine

Cysteine

Författare

Hong Yang

Kungliga Tekniska Högskolan (KTH)

Xiangyu Li

Bash Biotech Inc.

Kungliga Tekniska Högskolan (KTH)

Han Jin

Kungliga Tekniska Högskolan (KTH)

Hasan Turkez

Atatürk Üniversitesi

Gurkan Ozturk

Istanbul Medipol Universitesi

Hamdi Levent Doganay

VM Medicalpark Pendik Hospital Orthopedics and Traumatology

Bahçeşehir Üniversitesi

Cheng Zhang

Kungliga Tekniska Högskolan (KTH)

Jens B Nielsen

BioInnovation Institute

Chalmers, Life sciences, Systembiologi

Mathias Uhlen

Kungliga Tekniska Högskolan (KTH)

Jan Borén

Göteborgs universitet

Adil Mardinoglu

King's College London

Kungliga Tekniska Högskolan (KTH)

Free Radical Biology and Medicine

0891-5849 (ISSN) 18734596 (eISSN)

Vol. 204 347-358

Ämneskategorier

Neurologi

DOI

10.1016/j.freeradbiomed.2023.05.013

PubMed

37245532

Mer information

Senast uppdaterat

2023-06-21