第444次SKLBE学术论坛（瑞典皇家理工学院 张成教授）

报告人：Royal Institute of Technology (KTH), Sweden (瑞典皇家理工学院)

  Cheng Zhang (张成)

题目：  The effect of naturally occurring metabolic cofactor supplementation to decrease human liver fat 

                (通过补充天然代谢辅因子降低人体肝脏脂肪的效用)
时间：    2018-12-13   10:00-11:00
地点：    实验18楼315室

主持人：花强 教授

简历：

Sept 2007 - Aug 2011: Bachelor of Engineering in Bioengineering, East China University of Science and Technology (ECUST), China

Sept 2011 - Aug 2015: PhD in Engineering (Computational Biology), East China University of Science and Technology (ECUST), China

Sept 2013 - Aug 2015: Visiting PhD student in (Systems Biology), Chalmers University of Technology, Sweden

Sept 2015 - Aug 2016: Postdoctoral Researcher, Science for Life Laboratory, Royal Institute of Technology (KTH), Sweden

Sept 2016 - To Date: Senior Researcher, Science for Life Laboratory, Royal Institute of Technology (KTH), Sweden

摘要：

The prevalence of non-alcoholic fatty liver disease (NAFLD) is continue rising, and is becoming a worldwide public health problem. Here, we recruited 86 subjects with varying degree of hepatic steatosis (HS), detected the level of plasma metabolites and quantified the secretion rate of the very low-density lipoproteins for elucidating the molecular mechanisms underlying NAFLD. We investigated the metabolic differences in the liver tissue of subjects accounting the interactions between the liver, adipose and muscle tissues as well as red blood cells through personalized genome scale metabolic modelling. Our systems level analysis demonstrated that plasma and liver tissue level of serine, glycine and associated metabolites are downregulated in subjects with NAFLD and glycine is the limiting substrate for the synthesis of the glutathione. We found that the liver functions of the subjects with HS are significantly improved after the supplementation of the serine and hereby proposed a strategy for protecting against the progression of NAFLD.

We also performed a 5-day calibration study by supplementing metabolic cofactors including serine, N-acetyl-L-cysteine (NAC), nicotinamide riboside (NR) and l-carnitine, and measured the kinetics of these metabolites in the plasma of the subjects. We measured clinical parameters and observed no potential immediate side effects. Next we generated untargeted metabolomics data to reveal the changes associated with the supplementation of these metabolic cofactors using genome-scale metabolic modelling and observed that such supplementation is significantly associated with the lipid, amino acid and anti-oxidant metabolism. We also generated an ordinary differential equation (ODE) model to predict blood concentrations during daily long-term supplementation of the substances and liver concentrations using pharmacokinetic (PK) modeling to adjust the dose of the metabolic cofactors. We observed that supplementation of these metabolic cofactors may provide a therapeutic strategy for NAFLD progression by promoting the uptake and oxidation of fat in mitochondria and proposed its testing in randomized double blind placebo control human studies.