A5080818741- Drug Transport and Resistance Mechanisms
- Peroxisome Proliferator-Activated Receptors
- Liver Disease Diagnosis and Treatment
- Cholesterol and Lipid Metabolism
- Pancreatic function and diabetes
- Diabetes and associated disorders
- Retinoids in leukemia and cellular processes
- Endoplasmic Reticulum Stress and Disease
- Adipose Tissue and Metabolism
- Metabolism, Diabetes, and Cancer
- Diabetes Treatment and Management
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Genomics and Chromatin Dynamics
- Liver Diseases and Immunity
- Cancer, Lipids, and Metabolism
- Lipoproteins and Cardiovascular Health
- Fibroblast Growth Factor Research
- RNA Research and Splicing
- Cancer-related molecular mechanisms research
- RNA Interference and Gene Delivery
- Phytase and its Applications
- Liver physiology and pathology
- NF-κB Signaling Pathways
- Biomedical and Engineering Education
- Atherosclerosis and Cardiovascular Diseases
Université de Lille
2013-2024
Inserm
2012-2024
Institut Pasteur de Lille
2012-2024
Centre Hospitalier Universitaire de Lille
2017-2024
European Genomic Institute for Diabetes
2013-2015
Université Lille Nord de France
2009-2013
Institut Pasteur
2012
Genfit (France)
2005
Bile acids are signalling molecules, which activate the transmembrane receptor TGR5 and nuclear FXR. BA sequestrants (BAS) complex bile in intestinal lumen decrease FXR activity. The BAS–BA also induces glucagon-like peptide-1 (GLP-1) production by L cells potentiates β-cell glucose-induced insulin secretion. Whether is expressed controls GLP-1 unknown. Here, we show that activation decreases proglucagon expression interfering with glucose-responsive factor Carbohydrate-Responsive Element...
The recently discovered APOA5 gene has been shown in humans and mice to be important determining plasma triglyceride levels, a major cardiovascular disease risk factor. apoAV represents the first described apolipoprotein where overexpression lowers levels. Since fibrates represent commonly used therapy for lowering triglycerides humans, we investigated their ability modulate expression consequently influence Human primary hepatocytes treated with Wy 14,643 or fenofibrate displayed strong...
The nuclear bile acid receptor farnesoid X (FXR) is an important transcriptional regulator of acid, lipid, and glucose metabolism. FXR highly expressed in the liver intestine controls synthesis enterohepatic circulation acids. However, little known about FXR-associated proteins that contribute to metabolic regulation. Here, we performed a mass spectrometry-based search for FXR-interacting human hepatoma cells identified AMPK as coregulator FXR. interacted with nutrient-sensitive kinase...
The glucose-activated transcription factor carbohydrate response element binding protein (ChREBP) induces the expression of hepatic glycolytic and lipogenic genes. farnesoid X receptor (FXR) is a nuclear bile acid controlling acid, lipid, glucose homeostasis. FXR negatively regulates glycolysis lipogenesis in mouse liver. aim this study was to determine whether transcriptional activity ChREBP human hepatocytes unravel underlying molecular mechanisms. Agonist-activated inhibits...
Nonalcoholic fatty liver disease prevalence is soaring with the obesity pandemic, but pathogenic mechanisms leading to progression toward active nonalcoholic steatohepatitis (NASH) and fibrosis, major causes of liver-related death, are poorly defined. To identify key components during NASH we investigated transcriptome in a human cohort patients. The transition from histologically proven fibrosis was characterized by gene expression patterns that successively reflected altered functions...
CCCTC-binding factor (CTCF) is a ubiquitously expressed multifunctional transcription characterized by chromatin binding patterns often described as largely invariant. In this context, how CTCF recruitment and functionalities are used to promote cell type-specific gene expression remains poorly defined. Here, we show that, in addition constitutively bound sites (CTS), the cistrome comprises large proportion of showing highly dynamic during course adipogenesis. Interestingly, positively...
Bile acid metabolism is intimately linked to the control of energy homeostasis and glucose lipid metabolism. The nuclear receptor farnesoid X (FXR) plays a major role in enterohepatic cycling bile acids, but impact nutrients on poorly characterized. Metabolically active hepatocytes cope with increases intracellular concentrations by directing into storage (glycogen) or oxidation (glycolysis) pathways, as well pentose phosphate shunt hexosamine biosynthetic pathway. Here we studied whether...
Article14 May 2020Open Access Endoplasmic reticulum stress actively suppresses hepatic molecular identity in damaged liver Vanessa Dubois orcid.org/0000-0001-8894-2980 Inserm, CHU Lille, Institut Pasteur de U1011-EGID, University of France Search for more papers by this author Céline Gheeraert Wouter Vankrunkelsven orcid.org/0000-0003-0943-043X Clinical Division and Laboratory Intensive Care Medicine, Department Cellular Molecular KU Leuven, Belgium Julie Dubois-Chevalier Hélène Dehondt...
Obesity is associated with metabolic dysfunction of white adipose tissue (WAT). Activated adipocytes secrete pro-inflammatory cytokines resulting in the recruitment macrophages, which contribute to WAT insulin resistance. The bile acid (BA)-activated nuclear Farnesoid X Receptor (FXR) controls systemic glucose and lipid metabolism. Here, we studied role FXR function.
Alterations in the expression of recently discovered apolipoprotein A5 gene strongly affect plasma triglyceride levels. In this study, we investigated contribution APOA5 to liver X receptor (LXR) ligand-mediated effect on Following treatment with LXR ligand T0901317, found that mRNA levels were decreased hepatoma cell lines. The observation no down-regulation promoter activity was obtained by LXR-retinoid (RXR) co-transfection prompted us explore possible involvement known target SREBP-1c...
Metabolic diseases reach epidemic proportions. A better knowledge of the associated alterations in metabolic pathways liver is necessary. These studies need vitro human cell models. Several hepatoma models are used, but response many to physiological stimuli often lost. Here, we characterize two hepatocyte lines, IHH and HepaRG, by analysing expression regulation genes involved glucose lipid metabolism. Our results show that glycolysis pathway activated insulin both lines. Gluconeogenesis...
Adipocyte differentiation and function relies on a network of transcription factors, which is disrupted in obesity-associated low grade, chronic inflammation leading to adipose tissue dysfunction. In this context, there need for thorough understanding the transcriptional regulatory involved pathophysiology. Recent advances functional annotation genome has highlighted role non-coding RNAs cellular processes coordination with factors. Using an unbiased genome-wide approach, we identified...
Clinical data identified an association between the use of HMG-CoA reductase inhibitors (statins) and incident diabetes in patients with underlying risk factors such as obesity, hypertension dyslipidemia. The molecular mechanisms however are unknown. An observational cross-sectional study included 910 severely obese patients, mean (SD) body mass index (BMI) 46.7 (8.7), treated or without statins (ABOS cohort: a biological atlas severe obesity). Data sample collection took place France 2006...
The newly identified apolipoprotein A5 (APOA5), selectively expressed in the liver, is a crucial determinant of plasma triglyceride levels. Because elevated concentrations constitute an independent risk factor for cardiovascular diseases, it important to understand how expression this gene regulated. In present study, we retinoic acid receptor-related orphan receptor-alpha (RORalpha) as regulator human APOA5 expression.Using electromobility shift assays, first demonstrated that RORalpha1 and...
Control of gene transcription relies on concomitant regulation by multiple transcriptional regulators (TRs). However, how recruitment a myriad TRs is orchestrated at cis -regulatory modules (CRMs) to account for coregulation specific biological pathways only partially understood. Here, we have used mouse liver CRMs involved in regulatory activities the hepatic TR, NR1H4 (FXR; farnesoid X receptor), as our model system tackle this question. Using integrative cistromic, epigenomic,...
Apolipoprotein A-V is an important determinant of plasma triglyceride level in both humans and mice. This study showed the physiological impact apoA-V on insulin secretion rat pancreatic β-cells (INS-1 cells). In order to precise mechanism action, binding experiments coupled mass spectrometry were performed identify a potential membrane receptor. Results interaction between midkine protein. Confocal microscopy confirmed co-localisation this two-proteins after treatment INS-1 cells with...