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Kinetics of Metabolic Cofactors in NAFLD

Straipsnius versti gali tik registruoti vartotojai
Prisijungti Registracija
Nuoroda įrašoma į mainų sritį
StatusasBaigta
Rėmėjai
Sahlgrenska University Hospital, Sweden
Bendradarbiai
Karolinska Institutet
Chalmers University of Technology

Raktažodžiai

Santrauka

There is a strong correlation between major adverse health consequences of obesity and development of non-alcoholic fatty liver disease (NAFLD). NAFLD is characterized by abnormal hepatic accumulation of triglycerides and other lipids. It has become a worldwide health problem that accelerates cirrhosis, type 2 diabetes mellitus (T2DM), and especially premature cardiovascular morbidity and mortality.
The plasma level of glutathione (GSH) is typically depleted in individuals with metabolism related disorders. However, cellular GSH levels cannot be increased by supplementing GSH and it must be synthesized within the liver either de novo or by salvation pathway. The level of GSH is not enough to maintain and regulate the thiol redox status of the liver in subjects with high hepatic steatosis at fasting stage due to the depletion of glycine. Glycine can be synthesized via the interconversion of serine. It has been shown that the serine synthesis is downregulated in patients with NAFLD and supplementation of serine has attenuated alcoholic fatty liver by enhancing homocysteine metabolism in mice and rats. Depleted liver glutathione is also restored by the administration of N-acetylcystein as in acetaminophen poising. L-carnitine and nicotinamide that both stimulate the transfer of fatty acids from cytosol to mitochondria have been identified as two additional cofactors that are depleted in patients with NAFLD.
In this study, the kinetics in blood of pivotal metabolic cofactors, serine, L-carnitine, N-acetylcystein and nicotinamide after single and simultaneous dietary supplementation, are measured.

apibūdinimas

In 10 healthy subjects with BMI <30 kg/m2 the plasma concentrations of 4 natural compounds (nicotinamide riboside, L-carnitine, L-serine and N-acetylcystein) are measured by ultra-performance liquid chromatography-tandem mass spectrometry (UPLCMSMS) after individual and combined administration, on five consecutive days and at every hour during 9 hours after administration. The study will start at 8:00 every morning and at each time point, blood samples will be collected.

The taste and any potential sensing of the co-factors such as vertigo, nausea, bowel movement will be recorded.

Each participant will receive one oral dose of Day 1: 1 g nicotinamide riboside; Day 2: 3 g L-carnitine; Day 3: 5 g N-acetylcystein; Day 4: 20 g L-serine; Day 5: combined 1 g nicotinamide riboside, 3 g L-carnitine, 5 g N-acetylcystein, and 20 g L-serine

In addition, untargeted metabolomics analysis as well as O-link proteomics analysis we be performed to study effect of the administered cofactors.

Datos

Paskutinį kartą patikrinta: 01/31/2019
Pirmasis pateikimas: 02/03/2019
Numatytas registravimas pateiktas: 02/10/2019
Pirmas paskelbtas: 02/11/2019
Paskutinis atnaujinimas pateiktas: 02/11/2019
Paskutinis atnaujinimas paskelbtas: 02/14/2019
Faktinė studijų pradžios data: 08/31/2018
Numatoma pirminio užbaigimo data: 10/31/2018
Numatoma studijų užbaigimo data: 11/30/2018

Būklė ar liga

Healthy

Intervencija / gydymas

Dietary Supplement: Intervention

Fazė

-

Rankų grupės

RankaIntervencija / gydymas
Experimental: Intervention
Oral administration of cofactors, 1g nicotinamide riboside, 3g L-carnitine, 20g serine and 5g N-acetylcystein, first as single compounds, then combined, on 5 days
Dietary Supplement: Intervention
Oral administration of 1g nicotinamide riboside, 3g L-carnitine, 20g serine and 5g N-acetylcystein, first as single compounds, then combined, on 5 days

Tinkamumo kriterijai

Amžius, tinkami studijuoti 18 Years Į 18 Years
Tinkamos studijoms lytysMale
Priima sveikus savanoriusTaip
Kriterijai

Inclusion Criteria:

Healthy without any medication, no smokers, no obesity

Exclusion Criteria:

Any known disease, obesity

Rezultatas

Pirminės rezultatų priemonės

1. Changes of plasma levels of nicotinamide riboside measured by mass spectrometry [Twenty-four hours after administration]

Plasma levels of nicotinamide riboside by UPLCMSMS at 8 time points during 24h after administration

2. Changes of plasma levels of L-carnitine measured by mass spectrometry [Twenty-four hours after administration]

Plasma levels of L-carnitine (nM) measured by UPLCMSMS at 8 time points during 24h after administration

3. Changes of plasma levels of L-serine measured by mass spectrometry [Twenty-four hours after administration]

Plasma levels of L-serine (nM) measured by UPLCMSMS at 8 times points during 24h after administration

4. Changes of plasma levels of N-acetylcystein measured by mass spectrometry [Twenty-four hours after administration]

Plasma levels of N-acetylcystein (nM) measured by UPLCMSMS at 8 times points during 24h after administration

Antrinės rezultatų priemonės

1. Changes in the plasma level of metabolites associated with the supplementation of metabolic co-factors. [Twenty-four hours after administration of combined cofactors]

Untargeted metabolomic analysis using mass spectrometry. (Untargeted = not pre-specified in terms of outcome)

2. Changes in the plasma level of inflammation-related proteins associated with the supplementation of metabolic co-factors. [Twenty-four hours after administration of combined cofactors]

Changes in the plasma level of inflammation related proteins associated with the supplementation of metabolic co-factors.

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