A5081536133- Nuclear Structure and Function
- Pancreatic function and diabetes
- Lipoproteins and Cardiovascular Health
- Metabolism, Diabetes, and Cancer
- RNA Research and Splicing
- Adipose Tissue and Metabolism
- Peroxisome Proliferator-Activated Receptors
- Adipokines, Inflammation, and Metabolic Diseases
- Cancer, Lipids, and Metabolism
- Diabetes and associated disorders
- Lipid metabolism and biosynthesis
- Cholesterol and Lipid Metabolism
- Diabetes Treatment and Management
- Bariatric Surgery and Outcomes
- Diet and metabolism studies
- Endoplasmic Reticulum Stress and Disease
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Lipid metabolism and disorders
- Cardiovascular Disease and Adiposity
- Liver Disease Diagnosis and Treatment
- RNA and protein synthesis mechanisms
- Drug Transport and Resistance Mechanisms
- Nutritional Studies and Diet
- Caveolin-1 and cellular processes
- Nutrition and Health in Aging
Inserm
2015-2024
Centre National de la Recherche Scientifique
2015-2024
Nantes Université
2015-2024
Institut du Thorax
2015-2024
Centre Hospitalier Universitaire de Nantes
2013-2016
University of Cambridge
2007-2015
Wellcome/MRC Institute of Metabolic Science
2014-2015
Université Toulouse III - Paul Sabatier
2013
SUNY Downstate Health Sciences University
2013
Toxalim Research Centre in Food Toxicology
2013
Variants in the FTO (fat mass and obesity associated) gene are associated with increased body index humans. Here, we show by bioinformatics analysis that shares sequence motifs Fe(II)- 2-oxoglutarate–dependent oxygenases. We find recombinant murine Fto catalyzes 2OG-dependent demethylation of 3-methylthymine single-stranded DNA, concomitant production succinate, formaldehyde, carbon dioxide. Consistent a potential role nucleic acid demethylation, localizes to nucleus transfected cells....
Obesity-associated insulin resistance is characterized by a state of chronic, low-grade inflammation that associated with the accumulation M1 proinflammatory macrophages in adipose tissue. Although different evidence explains mechanisms linking expansion tissue and macrophage (ATM) polarization, current study we investigated concept lipid-induced toxicity as pathogenic link could explain trigger this response.
Transintestinal cholesterol excretion (TICE) is an alternate pathway to hepatobiliary secretion. Our study aimed at identifying molecular mechanisms of TICE.We studied TICE ex vivo in mouse and human intestinal explants, after bile diversion cannulation mice. We provide the first evidence that both low-density lipoprotein (LDL) high-density deliver for jejunal explants basolateral side. Proprotein convertase subtilisin kexin type 9 (PCSK9)(-/-) mice show increased LDL-TICE, acute injection...
Type 2 diabetes mellitus (T2DM) is a well-recognized independent risk factor for heart failure. T2DM associated with altered cardiac energy metabolism, leading to ectopic lipid accumulation and glucose overload, the exact contribution of these two parameters remaining unclear. To provide new insight into mechanism driving development diabetic cardiomyopathy, we studied unique model T2DM: lipodystrophic Bscl2−/− (seipin knockout [SKO]) mice. Echocardiography magnetic resonance imaging...
Deficiency of the endoplasmic reticulum (ER) protein seipin results in generalized lipodystrophy by incompletely understood mechanisms. Here, we report mitochondrial abnormalities seipin-deficient patient cells. A subset is enriched at ER-mitochondria contact sites (MAMs) human and mouse cells localizes vicinity calcium regulators SERCA2, IP3R, VDAC. Seipin association with MAM stimulated fasting-like stimuli, while lipid droplets promoted loading. Acute removal does not alter ER stores but...
β-Catenin is a key mediator of the Wnt pathway, which plays critical role in embryogenesis and oncogenesis. As transcriptional activator, β-catenin binds transcription factors, T-cell factor lymphoid enhancer factor, regulates gene expression response to signaling. Abnormal activation has been linked various types cancer. In yeast two-hybrid screen, we identified four half LIM-only protein 2 (FHL2) as novel β-catenin-interacting protein. Here show specific interaction FHL2 with β-catenin,...
Recent evidence supporting that adipose tissue (AT)-derived extracellular vesicles (EVs) carry an important part of the AT secretome led us to characterize EV-adipokine profile. In addition evidencing a high AT-derived EV secretion ability is further increased by obesity, we identify enrichment oligomeric forms adiponectin in small EVs (sEVs). This adipokine mainly distributed at external surface as result nonspecific adsorption soluble adiponectin. also constitute stable conveyors blood...
The metabolic effects of leptin may involve both centrally and peripherally mediated actions with a component the central potentially independent alterations in food intake. Ob/ob mice have significant abnormalities lipid metabolism, correctable by administration. We used ob/ob to study relative importance subtypes (central vs. peripheral; intake dependent independent) on metabolism. Mice were treated for 3 d leptin, either [intracerebroventricular (icv)] or (ip), compared pair-fed...
The apolipoprotein AV gene (APOA5) is a key determinant of plasma triglyceride levels, major risk factor for coronary artery disease and biomarker the metabolic syndrome. Since thyroid hormones influence very low density lipoprotein metabolism clinical studies have demonstrated an inverse correlation between status we examined whether APOA5 regulated by hormone. Here report that 3,5,3′-triiodo-l-thyronine (T3) synthetic receptor β (TRβ) ligand increase mRNA protein levels in hepatocytes. Our...
Whereas the role of thyroid hormone is clearly established in regulation cholesterol homeostasis, its involvement control serum triglyceride (TG) levels remains largely debated. Angiopoietin-like proteins 3 and 4 have recently been characterized as potent lipoprotein lipase inhibitors therefore important components plasma homeostasis. In present study, both ANGPTL4 ANGPTL3 gene expression was investigated. vivo studies revealed that down-regulates but not hypothyroid rats. Using receptor...
Significance Chronic low-grade inflammation plays a causative role in obesity-associated metabolic diseases. However, the mechanisms underlying chronicity of remain elusive. Herein, we identify inhibitor κB kinase epsilon (IKBKE) as new modulator chronic macrophages. We first show that IKBKE is clinically relevant distinct tissues associated with diseases including obesity, nonalcoholic steatohepatitis, and atherosclerosis. In all cases, expression predominates macrophages associates...
Lipid droplets store neutral lipids, primarily triacylglycerol and steryl esters. Seipin plays a role in lipid droplet biogenesis is thought to determine the site of size newly formed droplets. Here we show seipin-independent pathway biogenesis. In silico vitro experiments reveal that retinyl esters have intrinsic propensity sequester nucleate bilayers. Production mammalian yeast cells do not normally produce causes formation droplets, even strain produces only no other lipids. does or...
We have recently reported the first naturally occurring missense mutations in leptin receptor (LR) patients with severe obesity. examined molecular mechanisms by which these extracellular domain disrupt LR signaling. The Ala409Glu mutant is expressed at cell surface, binds normally but fails to signal downstream pathways. A409 present on surface-exposed region of Ig-like that forms binding site III for interaction leptin. This does not appear contribute affinity its critical activation...
Glucose intolerance and dyslipidaemia are independent risk factors for endothelium dysfunction CVD. The aim of the present study was to analyse preventive effect n -3 PUFA (EPA DHA) on lipid carbohydrate disturbances endothelial dysfunction. Three groups adult hamsters were studied 20 weeks: (1) control diet (Control); (2) high-fat (HF); (3) enriched with (HF -3) groups. increase in body weight fat mass HF compared Control group ( P < 0·05) not found group. Muscle TAG content similar...
Objective: Increased postprandial lipemia (PPL) is an independent risk factor for atherosclerotic cardiovascular diseases. PCSK9 (Proprotein convertase subtilisin kexin type 9) endogenous inhibitor of the LDLR (low-density lipoprotein receptor) pathway. We previously showed that inhibition in mice reduces PPL. However, relative contribution intracellular intestinal or liver-derived circulating to this effect still unclear. Approach and Results: To address issue, we generated first...
The recently discovered apolipoprotein AV (apoAV) gene has been reported to be a key player in modulating plasma triglyceride levels. Here we identify the hepatocyte nuclear factor-4alpha (HNF-4alpha) as novel regulator of human apoAV gene. Inhibition HNF-4alpha expression by small interfering RNA resulted down-regulation apoAV. Deletion, mutagenesis, and binding assays revealed that directly regulates promoter through DR1 [a direct repeat separated one nucleotide (nt)], via element for...