A5058920071- Liver Disease Diagnosis and Treatment
- Cholesterol and Lipid Metabolism
- Metabolism, Diabetes, and Cancer
- Pancreatic function and diabetes
- Lipid metabolism and biosynthesis
- Cancer, Hypoxia, and Metabolism
- Liver physiology and pathology
- Lipid metabolism and disorders
- Adipose Tissue and Metabolism
- Diet, Metabolism, and Disease
- Cancer-related Molecular Pathways
- FOXO transcription factor regulation
- Peroxisome Proliferator-Activated Receptors
- RNA modifications and cancer
- Cancer, Lipids, and Metabolism
- Endoplasmic Reticulum Stress and Disease
- Drug Transport and Resistance Mechanisms
- Epigenetics and DNA Methylation
- Adipokines, Inflammation, and Metabolic Diseases
- Cancer-related gene regulation
- Diabetes and associated disorders
- Pediatric Hepatobiliary Diseases and Treatments
- Diabetes Treatment and Management
- Histone Deacetylase Inhibitors Research
- Error Correcting Code Techniques
Inserm
2008-2024
Institut des Maladies Métaboliques et Cardiovasculaires
2018-2024
Université de Toulouse
2022-2024
Université Toulouse III - Paul Sabatier
2021-2024
University of Lausanne
2013-2023
SIB Swiss Institute of Bioinformatics
2021
Laboratoire de Mathématiques d'Orsay
2012-2017
Université de Montréal
2006-2017
Université Paris Cité
2007-2013
Centre National de la Recherche Scientifique
2007-2013
Nonalcoholic fatty liver disease (NAFLD) is associated with all features of the metabolic syndrome. Although deposition excess triglycerides within cells, a hallmark NAFLD, loss insulin sensitivity, it not clear which cellular abnormality arises first. We have explored this in mice overexpressing carbohydrate responsive element–binding protein (ChREBP). On standard diet, ChREBP remained sensitive, despite increased expression genes involved lipogenesis/fatty acid esterification and resultant...
The transcription factor carbohydrate-responsive element–binding protein (ChREBP) has emerged as a central regulator of lipid synthesis in liver because it is required for glucose-induced expression the glycolytic enzyme liver–pyruvate kinase (L-PK) and acts synergy with SREBP to induce lipogenic genes such acetyl-CoA carboxylase (ACC) fatty acid synthase (FAS). Liver X receptors (LXRs) are also important regulators pathway, recent finding that ChREBP direct target LXRs glucose itself can...
β-catenin signaling can be both a physiological and oncogenic pathway in the liver. It controls compartmentalized gene expression, allowing liver to ensure its essential metabolic function. is activated by mutations 20%-40% of hepatocellular carcinomas (HCCs) with specific features. We decipher molecular determinants β-catenin-dependent zonal transcription using mice β-catenin-activated or -inactivated hepatocytes, characterizing vivo their chromatin occupancy T-cell factor (Tcf)−4...
E2F transcription factors are known regulators of the cell cycle, proliferation, apoptosis, and differentiation. Here, we reveal that E2F1 plays an essential role in liver physiopathology through regulation glycolysis lipogenesis. We demonstrate deficiency leads to a decrease de novo synthesis fatty acids hepatocytes. further directly binds promoters key lipogenic genes, including Fasn, but does not bind genes encoding pathway components, suggesting indirect effect. In murine models,...
Insulin resistance is a fundamental pathogenic factor that characterizes various metabolic disorders, including obesity and type 2 diabetes. Adipose tissue contributes to the development of obesity-related insulin through increased release fatty acids, altered adipokine secretion, and/or macrophage infiltration cytokine release. Here, we aimed analyze participation cyclin-dependent kinase 4 (CDK4) in adipose biology. We determined white (WAT) from CDK4-deficient mice exhibits impaired...
β-Klotho (encoded by Klb) is the obligate coreceptor mediating FGF21 and FGF15/19 signaling. Klb-/- mice are refractory to beneficial action of pharmacological treatment including stimulation glucose utilization thermogenesis. Here, we investigated energy homeostasis in on high-fat diet order better understand consequences abrogating both endogenous signaling during caloric overload. Surprisingly, resistant diet-induced obesity (DIO) owing enhanced expenditure BAT activity. exhibited not...
Cholesterol accumulation in the liver is an early event nonalcoholic fatty disease (NAFLD). Here, we demonstrate that E2F1 plays a crucial role maintaining cellular cholesterol homeostasis by regulating uptake via proprotein convertase subtilisin/kexin 9 (PCSK9), enzyme promotes low-density lipoprotein receptor (LDLR) degradation upon activation. E2f1-/- mice display reduced total plasma levels and increased content liver. In this study, show E2f1 deletion mouse models leads to marked...
Introduction Adipose tissue is considered an important metabolic tissue, in charge of energy storage as well being able to act systemic homeostasis and inflammation. Epigenetics involves a series factors that are for gene regulation or chromatin structure, mostly DNA methylation histone-tail modifications, which can be modified by environmental conditions (nutrition, lifestyle, smoking…). Since diseases like obesity diabetes closely related lifestyle nutrition, epigenetic deregulation could...
Aberrant hepatic glucose production contributes to the development of hyperglycemia and is a hallmark type 2 diabetes. In recent study, we showed that transcription factor E2F1, component cell cycle machinery, steatosis through transcriptional regulation key lipogenic enzymes. Here, investigate if E2F1 by regulating gluconeogenesis. We use different genetic models regulates gluconeogenesis in primary hepatocytes vivo. study impact depleting or inhibiting activity diabetic mouse evaluate this...
The endoplasmic reticulum (ER) unfolded protein response (UPR(er)) pathway plays an important role in helping pancreatic β cells to adapt their cellular responses environmental cues and metabolic stress. Although altered UPR(er) gene expression appears rodent human type 2 diabetic (T2D) islets, the underlying molecular mechanisms remain unknown. We show here that germline cell-specific disruption of lysine acetyltransferase 2B (Kat2b) mice leads impaired insulin secretion glucose...
Metabolic diseases such as obesity and type 2 diabetes are recognized independent risk factors for hepatocellular carcinoma (HCC). Hyperinsulinemia, a hallmark of these pathologies, is suspected to be involved in HCC development. The molecular adapter growth factor receptor binding protein 14 (Grb14) an inhibitor insulin catalytic activity, highly expressed the liver. To study its involvement hepatocyte proliferation, we specifically inhibited liver expression using short hairpin RNA...
Lipids are essential cellular constituents that have many critical roles in physiological functions. They notably involved energy storage and cell signaling as second messengers, they major of membranes, including lipid rafts. As a consequence, implicated large number heterogeneous diseases, such cancer, diabetes, neurological disorders, inherited metabolic diseases. Due to the high structural diversity complexity species, presence isomeric isobaric their occurrence at concentration scale,...
Dysregulations of lipid metabolism in the liver may trigger steatosis progression, leading to potentially severe clinical consequences such as nonalcoholic fatty diseases (NAFLDs). Molecular mechanisms underlying lipogenesis are very complex and fine-tuned by chromatin dynamics multiple key transcription factors. Here, we demonstrate that nuclear factor HMGB1 acts a strong repressor lipogenesis. Mice with liver-specific Hmgb1 deficiency display exacerbated steatosis, while...
Cyclin-dependent kinases (CDKs) are emerging regulators of adipose tissue metabolism. Here we aimed to explore the role CDK7 in thermogenic fat. We found that brown (BAT)-specific knockout mice (Cdk7bKO) have decreased BAT mass and impaired β3-adrenergic signaling develop hypothermia upon cold exposure. loss disrupts induction genes response cold. However, Cdk7bKO do not show systemic metabolic dysfunction. Increased expression creatine metabolism compensates for heat generation Finally, is...
The loss of pancreatic β-cell identity has emerged as an important feature type 2 diabetes development, but the molecular mechanisms are still elusive. Here, we explore cell-autonomous role cell-cycle regulator and transcription factor E2F1 in maintenance identity, insulin secretion, glucose homeostasis. We show that β-cell–specific E2f1 function mice triggers intolerance associated with defective altered endocrine cell mass, downregulation many genes, concomitant increase non–β-cell...
Chromatin immunoprecipitation (ChIP) has gained importance to identify links between the genome and proteome. Adipose tissue emerged as an active tissue, which secretes a wide range of molecules that have been related metabolic obesity-related disorders, such diabetes, cardiovascular failure, syndrome, or cancer. In turn, epigenetics raised in discerning possible relationship lifestyle environment. However, ChIP application human adipose is limited by several factors, sample size, frozen...