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Combined Metabolic Cofactor Supplementation Reduces Liver Fat in Nonalcoholic Fatty Liver Disease

61 Pages Posted: 2 Feb 2021 Publication Status: Review Complete

See all articles by Mujdat Zeybel

Mujdat Zeybel

University of Nottingham - NIHR Nottingham Biomedical Research Centre

Ozlem Altay

Royal Institute of Technology (KTH) - Science for Life Laboratory (SciLife Lab)

Muhammad Arif

Royal Institute of Technology (KTH) - Science for Life Laboratory

Xiangyu Li

Royal Institute of Technology (KTH) - Science for Life Laboratory (SciLife Lab)

Hong Yang

Royal Institute of Technology (KTH) - Science for Life Laboratory (SciLife Lab)

Claudia Fredolini

Royal Institute of Technology (KTH) - Science for Life Laboratory (SciLife Lab)

Murat Akyildiz

Koç University - Department of Gastroenterology and Hepatology

Burcin Saglam

Koç University - Department of Gastroenterology and Hepatology

Mehmet Gokhan Gonenli

Koç University - Department of Gastroenterology and Hepatology

Dilek Ural

Koç University - School of Medicine

Woonghee Kim

Royal Institute of Technology (KTH) - Science for Life Laboratory (SciLife Lab)

Jochen M. Schwenk

Royal Institute of Technology (KTH) - Science for Life Laboratory (SciLife Lab)

Cheng Zhang

Royal Institute of Technology (KTH) - Science for Life Laboratory

Saeed Shoaie

King's College London - Centre for Host-Microbiome Interactions

Jens Nielsen

Chalmers University of Technology - Department of Biology and Biological Engineering

Mathias Uhlen

Royal Institute of Technology (KTH) - Science for Life Laboratory

Jan Boren

University of Gothenburg - Department of Molecular and Clinical Medicine

Adil Mardinoglu

Royal Institute of Technology (KTH) - Science for Life Laboratory

More...

Abstract

We have previously found that combined metabolic cofactor supplementation (CMCS) 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 CMCS in Nonalcoholic fatty liver disease (NAFLD) patients in a placebo-controlled 10-week study. We found that CMCS 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 metagenomics 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 observed that CMCS could develop a pharmacological treatment strategy in NAFLD patients.

Keywords: Nonalcoholic fatty liver disease, CMCS, Metabolomics, Proteomics, gut and oral metagenomics, Systems Medicine

Suggested Citation

Zeybel, Mujdat and Altay, Ozlem and Arif, Muhammad and Li, Xiangyu and Yang, Hong and Fredolini, Claudia and Akyildiz, Murat and Saglam, Burcin and Gonenli, Mehmet Gokhan and Ural, Dilek and Kim, Woonghee and Schwenk, Jochen M. and Zhang, Cheng and Shoaie, Saeed and Nielsen, Jens and Uhlen, Mathias and Boren, Jan and Mardinoglu, Adil, Combined Metabolic Cofactor Supplementation Reduces Liver Fat in Nonalcoholic Fatty Liver Disease. Available at SSRN: https://ssrn.com/abstract=3778301 or http://dx.doi.org/10.2139/ssrn.3778301
This version of the paper has not been formally peer reviewed.

Mujdat Zeybel

University of Nottingham - NIHR Nottingham Biomedical Research Centre ( email )

University Park
Nottingham, NG8 1BB
United Kingdom

Ozlem Altay

Royal Institute of Technology (KTH) - Science for Life Laboratory (SciLife Lab) ( email )

Lindstedtsvägen 30-100 44
Stockholm, SE-100 44
Sweden

Muhammad Arif

Royal Institute of Technology (KTH) - Science for Life Laboratory ( email )

Stockholm, SE-100 44
Sweden

Xiangyu Li

Royal Institute of Technology (KTH) - Science for Life Laboratory (SciLife Lab)

Lindstedtsvägen 30-100 44
Stockholm, SE-100 44
Sweden

Hong Yang

Royal Institute of Technology (KTH) - Science for Life Laboratory (SciLife Lab)

Lindstedtsvägen 30-100 44
Stockholm, SE-100 44
Sweden

Claudia Fredolini

Royal Institute of Technology (KTH) - Science for Life Laboratory (SciLife Lab) ( email )

Lindstedtsvägen 30-100 44
Stockholm, SE-100 44
Sweden

Murat Akyildiz

Koç University - Department of Gastroenterology and Hepatology

Law School
Rumelifeneri Yolu - Sariyer
Istanbul, 34450
Turkey

Burcin Saglam

Koç University - Department of Gastroenterology and Hepatology ( email )

Law School
Rumelifeneri Yolu - Sariyer
Istanbul, 34450
Turkey

Mehmet Gokhan Gonenli

Koç University - Department of Gastroenterology and Hepatology ( email )

Law School
Rumelifeneri Yolu - Sariyer
Istanbul, 34450
Turkey

Dilek Ural

Koç University - School of Medicine ( email )

Law School
Rumelifeneri Yolu - Sariyer
Istanbul, 34450
Turkey

Woonghee Kim

Royal Institute of Technology (KTH) - Science for Life Laboratory (SciLife Lab) ( email )

Lindstedtsvägen 30-100 44
Stockholm, SE-100 44
Sweden

Jochen M. Schwenk

Royal Institute of Technology (KTH) - Science for Life Laboratory (SciLife Lab) ( email )

Lindstedtsvägen 30-100 44
Stockholm, SE-100 44
Sweden

Cheng Zhang

Royal Institute of Technology (KTH) - Science for Life Laboratory ( email )

Stockholm, SE-100 44
Sweden

Saeed Shoaie

King's College London - Centre for Host-Microbiome Interactions ( email )

United Kingdom

Jens Nielsen

Chalmers University of Technology - Department of Biology and Biological Engineering ( email )

SE-412 96 Goteborg
Sweden

Mathias Uhlen

Royal Institute of Technology (KTH) - Science for Life Laboratory ( email )

Stockholm, SE-100 44
Sweden

Jan Boren

University of Gothenburg - Department of Molecular and Clinical Medicine ( email )

PO Box 400
Göteborg, SE405 30
Sweden

Adil Mardinoglu (Contact Author)

Royal Institute of Technology (KTH) - Science for Life Laboratory ( email )

Stockholm, SE-100 44
Sweden

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