A5101994869- Adipose Tissue and Metabolism
- Lipid metabolism and biosynthesis
- Adipokines, Inflammation, and Metabolic Diseases
- Caveolin-1 and cellular processes
- Cholesterol and Lipid Metabolism
- Peroxisome Proliferator-Activated Receptors
- Lipid metabolism and disorders
- Autophagy in Disease and Therapy
- Cancer, Lipids, and Metabolism
- Diet and metabolism studies
- Cardiovascular Disease and Adiposity
- Metabolism, Diabetes, and Cancer
- Regulation of Appetite and Obesity
- Erythrocyte Function and Pathophysiology
- Fatty Acid Research and Health
- Extracellular vesicles in disease
- Receptor Mechanisms and Signaling
- Liver Disease Diagnosis and Treatment
- Retinoids in leukemia and cellular processes
- Nuclear Structure and Function
- Pancreatic function and diabetes
- Lipid Membrane Structure and Behavior
- Gut microbiota and health
- Lipoproteins and Cardiovascular Health
- Plant responses to water stress
Sorbonne Université
2015-2025
Inserm
2016-2025
Nutrition et obésité : approches systémiques
2014-2025
Pitié-Salpêtrière Hospital
2014-2022
Fondation pour l’innovation en Cadiométabolisme et Nutrition
2014-2019
Biotherapy of Genetic Diseases, Inflammatory Disorders and Cancers
2019
Unité de recherche sur les maladies cardiovasculaires et métaboliques
1988-2017
Assistance Publique – Hôpitaux de Paris
2014-2015
Centre de Recherche des Cordeliers
2005-2014
Université Paris Cité
2007-2014
The transcription of genes encoding proteins involved in the hepatic synthesis lipids from glucose is strongly stimulated by carbohydrate feeding. It now well established that liver, main activator expression this group genes, with insulin having only a permissive role. While ADD1/SREBP-1 has been implicated lipogenic gene through temporal association food intake and ectopic gain-of-function experiments, no genetic evidence for requirement factor glucose-mediated established. We show here...
Context: Berardinelli-Seip congenital lipodystrophy (BSCL) is a rare recessive disease characterized by near absence of adipose tissue, resulting in severe dyslipidemia and insulin resistance. In most reported cases, BSCL due to alterations either seipin, unknown function, or 1-acylglycerol-3-phosphate acyltransferase-β (AGPAT2), which catalyzes the formation phosphatidic acid. Objective: We sought determine genetic origin unexplained cases BSCL. thus sequenced CAV1, encoding caveolin-1, as...
Thiazolidinediones are potent antidiabetic compounds, in both animal and human models, which act by enhancing peripheral sensitivity to insulin. high-affinity ligands for peroxisome proliferator-activated receptor-γ, a key factor adipocyte differentiation, they efficient promoters of differentiation vitro. Thus, it could be questioned whether thiazolidinedione therapy aimed at improving insulin would promote the recruitment new adipocytes vivo. To address this problem, we have studied vivo...
Enlarged fat cells exhibit modified metabolic capacities, which could be involved in the complications of obesity at whole body level. We show here that sterol regulatory element-binding protein 2 (SREBP-2) and its target genes are induced adipose tissue several models rodent obesity, suggesting cholesterol imbalance enlarged adipocytes. Within a particular pad, larger adipocytes have reduced membrane concentrations compared with smaller cells, demonstrating altered distribution is...
We have investigated the targeting of caveolin to lipid bodies in adipocytes that express high levels caveolins and contain well‐developed droplets. observed droplets isolated from caveolin‐1 knock out mice contained dramatically reduced cholesterol, indicating is required for maintaining cholesterol content this organelle. Analysis distribution by cell fractionation fluorescent light microscopy 3T3‐L1 indicated addition rapidly stimulated translocation The cholesterol‐induced trafficking...
Macrophages face a substantial amount of cholesterol after the ingestion apoptotic cells, and LIPA (lysosomal acid lipase) has major role in hydrolyzing cholesteryl esters endocytic compartment.Here, we directly investigated LIPA-mediated clearance cells both vitro vivo.We show that inhibition causes defective efferocytic response because impaired generation 25-hydroxycholesterol 27-hydroxycholesterol. Reduced synthesis contributed to mitochondria-associated membrane leading mitochondrial...
Adipose extracellular vesicles (AdEVs) transport lipids that could participate in the development of obesity-related metabolic dysfunctions. This study aims to define mouse AdEV lipid signature by a targeted LC-MS/MS approach either healthy or obesity context. Distinct clustering and visceral adipose tissue (VAT) lipidomes principal component analysis reveals specific sorting when compared with secreting VAT. Comprehensive identifies enrichment ceramides, sphingomyelins,...
We evaluated the hypothesis of sterol-regulatory element-binding protein (SREBP)-1c being a general mediator transcriptional effects insulin, with focus on adipocytes, in which insulin profoundly influences specific gene expression. Using real time quantitative reverse transcriptase-PCR to monitor changes expression about 50 genes that cover wide range adipocyte functions, we have compared impact treatment adenoviral overexpression either dominant positive or negative SREBP-1c mutants 3T3-L1...
Fatty acid synthase (FAS), a key lipogenic enzyme, is expressed in the two major sites of fatty production body, that is, liver and adipose tissue. Surprisingly, relative contribution these to lipogenesis highly variable among species. For example, besides situation rodents, where fat are equally active, some mammals such as pig occurs principally tissue, whereas avian species, main site. We addressed question concerning factors determining site synthesis. show expression adipocyte...
Elevated lipogenesis is a key determinant of exaggerated fat deposition in adipose tissue obese Zucker rats. We previously delineated region the fatty-acid synthase promoter, which was responsible for obesity-related overexpression (FAS) gene, by negatively regulating activity downstream promoter lean but not rat cells. The present study aimed to identify transcriptional factors acting on this target region. First, functional analysis mutated FAS constructs transiently transfected and...
Elevated ceramide concentrations in adipocytes and skeletal muscle impair PKB (protein kinase B; also known as Akt)-directed insulin signalling to key hormonal end points. An important feature of this inhibition involves the ceramide-induced activation atypical PKCzeta C-zeta), which associates with negatively regulates PKB. In present study, we demonstrate that is critically dependent on targeting subsequent retention PKCzeta-PKB within CEM (caveolin-enriched microdomains), facilitated by...
Caveolins form plasmalemnal invaginated caveolae. They also locate around intracellular lipid droplets but their role in this location remains unclear. By studying primary adipocytes that highly express caveolin-1, we characterized the impact of caveolin-1 deficiency on droplet proteome and lipidome. We identified several missing proteins surface caveolin-deficient showed pool is organized as multi-protein complexes containing cavin-1, with similar dynamics those found On side, caveolin did...
OBJECTIVE Ceramide is now recognized as a negative regulator of insulin signaling by impairing protein kinase B (PKB)/Akt activation. In different cells, two distinct mechanisms have been proposed to mediate ceramide inhibition PKB/Akt: one involving atypical C zeta (PKCζ) and the other phosphatase-2 (PP2A). We hypothesized that action through PKCζ or PP2A might depend on plasma membrane (PM) structural organization especially caveolin-enriched domain (CEM) abundance. RESEARCH DESIGN AND...
The abundance of epicardial adipose tissue (EAT) is associated with atrial fibrillation (AF), the most frequent cardiac arrhythmia. However, both origin and factors involved in EAT expansion are unknown. Here, we found that adult human cells were highly adipogenic through an epithelial-mesenchymal transition vitro vivo. In a genetic lineage tracing WT1CreERT2+/-RosatdT+/- mouse model subjected to high-fat diet, adipocytes derived from subset progenitors. Atrial myocardium secretome induces...
Adipose tissue dysfunction in obesity has been linked to low-grade inflammation causing insulin resistance. Transcriptomic studies have identified death-associated protein kinase 2 (DAPK2) among the most strongly downregulated adipose genes human obesity, but role of this is unknown. We show that mature adipocytes rather than stromal vascular cells mainly expressed DAPK2 and mRNA obese patients gradually recovered after bariatric surgery–induced weight loss. also high-fat diet–induced mice....
A serious metabolic syndrome combining insulin-resistance, dyslipidemia, central adiposity, and peripheral lipoatrophy has arisen in HIV-infected patients receiving highly active antiretroviral therapy. The aim of this work was to examine the effects nonnucleoside reverse transcriptase inhibitor (NNRTI) efavirenz on adipocyte differentiation metabolism. When induced differentiate presence (5–50 μm), 3T3-F442A preadipocytes failed accumulate cytoplasmic triacylglycerol droplets. This...
Adipocytes specialized in the storage of energy as fat are among most caveolae-enriched cell types. Loss caveolae produces lipodystrophic diabetes humans, which cannot be reversed by endothelial rescue caveolin expression mice, indicating major importance adipocyte caveolae. However, how participate functions is poorly understood. We investigated dynamic conditions lipid store fluctuations and demonstrate reciprocal regulation density droplet storage. identified caveolin-1 a crucial step...
The role of the ATP-binding cassette G1 (ABCG1) transporter in human pathophysiology is still largely unknown. Indeed, beyond its mediating free cholesterol efflux to HDL, ABCG1 equally promotes lipid accumulation a triglyceride (TG)-rich environment through regulation bioavailability lipoprotein lipase (LPL). Because both and LPL are expressed adipose tissue, we hypothesized that implicated adipocyte TG storage therefore could be major actor tissue fat accumulation. Silencing Abcg1...