Dr AICHA DEMIDEM

INSERM Researcher

Email : contact
Phone : +33(0)4 73 17 80 47

Research Activities

There is a rising incidence of Non Alcoholic Fatty Liver Disease (NAFLD) as well as of the frequency of Hepatocellular Carcinoma (HCC) associated with NAFLD which occurs in 40% of cases in the absence of cirrhosis. NAFLD is closely linked to obesity, type 2 diabetes, dyslipidemia and insulin resistance and considered as the liver manifestation of the metabolic syndrome. The putative metabolic pathways linking steatosis and steato-hepatitis to HCC were little investigated. There is no study reporting the impact of fibrosis on metabolic profile of HCC developed in NAFLD. The aim of our study is to highlight new biomarkers and propose metabolic pathways of HCC according to fibrosis stages (F0F1 versus F3F4).

** HCC metabolic features according to fibrosis level (F0F1 vs F3F4)

Tissues were collected from the French Liver Biobank. Among the 52 HCC, 26 were developed in severe fibrosis or cirrhosis (F3F4) and 26 no or mild fibrosis (F0F1). ¹H-NMR  metabolomic analysis combined to an optimization evolutionary method (genetic algorithm, Linear Discriminant Analysis and cross-validation) allowed to  reveal that HCC developed in  NAFLD without fibrosis F0F1,  an increase in the level of derivatives of choline corresponding to an alteration of phospholipid membranes synthesis and  increased levels of glutamine,  suggesting the activation of choline kinase and  glutamine synthetase respectively. In contrast, HCC-F3F4 developed in NAFLD with severe fibrosis or cirrhosis are characterized by an accumulation of branched amino acids suggesting an activation of the mTOR pathway. Our metabolomic analysis suggest for the first time that there are two phenotypes of HCC developed in NAFLD according to the fibrosis level. This study highlights the impact of underlying pathology on metabolic reprogramming of the tumor.

Publications

LECUYER L, DALLE C, LYAN B, DEMIDEM A, ROSSARY A, VASSON MP, PETERA M, LAGREE M, FERREIRA T, CENTENO D, GALAN P, HERCBERG S, DESCHASAUX M, PARTULA V, SROUR B, LATINO-MARTEL P, KESSE-GUYOT E, DRUESNE PECOLLO N, DURAND S, PUJOS-GUILLOT E, TOUVIER M. Plasma metabolomic signatures associated with long-term breast cancer risk in the SU.VI.MAX prospective cohort. Cancer Epidemiol Biomarkers Prev. 2019      

TEILHET C, REYNES C, SABATIER R, VASSON MP, ABERGEL A, DEMIDEM A. Human Hepatocellular Carcinoma metabolomic profile in Non Alcoholic Fatty Liver Disease (NAFLD) according to severity of fibrosis. Hepatol 2018, 80, 800-801.

MORVAN D, DEMIDEM A. NMR metabolomics of fibroblasts with inherited mitochondrial Complex I mutation reveals treatment-reversible lipid and amino acid metabolism alterations. Metabolomics. 2018: 14: (5)

TEILHET C, MORVAN D, JOUBERT-ZAKEYH J, BIESSE AS, PEREIRA B, MASSOULIER S, DECHELOTTE P, PEZET D, BUC E, LAMBLIN G, PEOC'H M, PORCHERON J, VASSON MP, ABERGEL A, DEMIDEM A. Specificities of human Hepatocellular Carcinoma developed on Non-Alcoholic Fatty Liver Disease in absence of cirrhosis revealed by tissue extracts ¹H-NMR Spectroscopy. Metabolites. 2017 ; 7, 4

MORVAN D, DEMIDEM A. Metabolomics and transcriptomics demonstrate severe oxidative stress in both localized chemotherapy-treated and bystander tumors. Biochim Biophys Acta. 2014; 1840:1092-104