- Adipose Tissue and Metabolism
- Nuclear Structure and Function
- HIV-related health complications and treatments
- Antioxidant Activity and Oxidative Stress
- Lipid metabolism and biosynthesis
- HIV Research and Treatment
- RNA Research and Splicing
- Cholesterol and Lipid Metabolism
- HIV/AIDS drug development and treatment
- Peroxisome Proliferator-Activated Receptors
- Adipokines, Inflammation, and Metabolic Diseases
- Atherosclerosis and Cardiovascular Diseases
- Metabolism, Diabetes, and Cancer
- Pancreatic function and diabetes
- Fatty Acid Research and Health
- Mitochondrial Function and Pathology
- Diabetes and associated disorders
- Bone health and treatments
- Cytomegalovirus and herpesvirus research
- Multiple Myeloma Research and Treatments
- Free Radicals and Antioxidants
- Dietary Effects on Health
- Biochemical Acid Research Studies
- Circadian rhythm and melatonin
- Cancer, Lipids, and Metabolism
Sorbonne Université
2016-2025
Inserm
2016-2025
Centre de Recherche Saint-Antoine
2016-2025
Fondation pour l’innovation en Cadiométabolisme et Nutrition
2013-2024
University of Graz
2024
University of Pennsylvania
2024
Assistance Publique – Hôpitaux de Paris
2010-2021
Hôpital Saint-Antoine
1990-2020
Université Sorbonne Nouvelle
2020
Centre National de la Recherche Scientifique
1982-2018
Perilipin is the most abundant adipocyte-specific protein that coats lipid droplets, and it required for optimal incorporation release from droplet. We identified two heterozygous frameshift mutations in perilipin gene (PLIN1) three families with partial lipodystrophy, severe dyslipidemia, insulin-resistant diabetes. Subcutaneous fat patients was characterized by smaller-than-normal adipocytes, macrophage infiltration, fibrosis. In contrast to wild-type perilipin, mutant forms of failed...
Protease inhibitors used in the treatment of HIV infection have been causally associated with lipodystrophy and insulin resistance were shown to alter adipocyte differentiation cultured cells. We aimed delineate mechanism by which indinavir impaired function. report that altered neither growth nor sensitivity 3T3-F442A preadipocytes, did it initial step their differentiation, i.e., clonal proliferation. However, adipose conversion was inhibited (by 50–60%), as 1) decrease number newly formed...
Dunnigan-type familial partial lipodystrophy (FPLD), characterized by an abnormal body fat redistribution with insulin resistance, is caused missense heterozygous mutations in A-type lamins (lamins A and C). A- B-type are ubiquitous intermediate filament proteins that polymerize at the inner face of nuclear envelope. We have analyzed primary cultures skin fibroblasts from three patients harboring R482Q or R482W mutations. These cells were euploid able to cycle divide. subpopulation these had...
Aging is associated with central fat redistribution and insulin resistance. To identify age-related adipose features, we evaluated the senescence adipogenic potential of adipose-derived stromal cells (ASCs) from abdominal subcutaneous obtained healthy normal-weight young (<25 years) or older women (>60 years). Increased cell passages young-donor ASCs (in vitro aging) resulted in but not oxidative stress. ASC-derived adipocytes presented impaired adipogenesis no early mitochondrial...
Objectives: To study whether HIV protease inhibitors could induce nuclear lamina alterations in adipocytes as observed a genetic form of lipodystrophy due to lamin A/C mutation. Design: We have previously that indinavir (IDV) impairs adipocyte differentiation and sterol regulatory element-binding protein-1 (SREBP-1) localization 3T3-F442A adipocytes. compared here the effects IDV with produced by two other PIs, nelfinavir (NFV) amprenavir (APV) on adipose conversion, cellular SREBP-1,...
Mutations in the LMNA gene are responsible for several laminopathies, including lipodystrophies, with complex genotype/phenotype relationships. OBJECTIVE, DESIGN, SETTING, AND PATIENTS: Sequencing of coding regions 277 unrelated adults investigated lipodystrophy and/or insulin resistance revealed 17 patients substitutions at codon 482 observed typical Dunnigan's familial partial and 10 other mutations. We report here phenotypes non-codon mutations compare them those 11 also studied skin...
Treatment of HIV-infected patients is associated with early onset aging-related comorbidities. Some the adverse effects antiretroviral therapy have been attributed to mitochondrial toxicity nucleoside reverse transcriptase inhibitors (NRTI), and it note that dysfunction oxidative stress are involved in aging processes. In this regard, we examined whether NRTIs could accelerate senescence cultured cells.Human fibroblasts were exposed from culture passage 1 14. Cytochrome c-oxidase (COX)...
Nucleoside analogues are suspected of playing a role in peripheral fat loss patients during long-term treatment with antiretroviral drugs.We compared the effects stavudine (10 microM), zidovudine (1 muM), didanosine abacavir (4 lamivudine and tenofovir near their maximum concentration values, on differentiation, lipid accumulation, survival mitochondrial function differentiating 3T3-F442A differentiated 3T3-L1 adipocytes.None nucleoside reverse transcriptase inhibitors (NRTI) markedly...
To determine whether and how protease inhibitors (PIs) could affect vascular aging.HIV therapy with PIs is associated an increased risk of premature cardiovascular disease. The effect ritonavir a combination lopinavir (for 30 days) on senescence, oxidative stress, inflammation was evaluated in human coronary artery endothelial cells (HCAECs). These HCAECs were either cotreated or not pravastatin farnesyl transferase inhibitor (FTI)-277 2 antioxidants (manganese [III] tetrakis [4-benzoic...
Objective— Inactivating peroxisome proliferator-activated receptor-γ (PPARγ) mutations lead to a syndrome of familial partial lipodystrophy (FPLD3) associated with early-onset severe hypertension. PPARγ can repress the vascular renin–angiotensin system (RAS) and angiotensin II receptor 1 expression. We evaluated relationships between inactivation cellular RAS using FPLD3 patients’ cells human smooth muscle expressing mutant or wild-type PPARγ. Approach Results— identified 2 novel PPAR G...
Identification of new adipokines that potentially link obesity to insulin resistance represents a major challenge. We recently showed NOV/CCN3, multifunctional matricellular protein, is synthesized and secreted by adipose tissue, with plasma levels highly correlated BMI. NOV involvement in tissue repair, fibrotic inflammatory diseases, cancer has been previously reported. However, its role energy homeostasis remains unknown. investigated the metabolic phenotype NOV−/− mice fed standard or...
For people living with HIV, treatment integrase-strand-transfer-inhibitors (INSTIs) can promote adipose tissue (AT) gain. We previously demonstrated that INSTIs induce hypertrophy and fibrosis in AT of macaques humans. By promoting energy expenditure, the emergence beige adipocytes white (beiging) could play an important role by limiting excess lipid storage associated adipocyte dysfunction. hypothesized alter via beiging inhibition. Fibrosis gene expression were measured subcutaneous (SCAT)...
Objective The lipodystrophy syndrome is a major adverse effect of highly active antiretroviral therapy (HAART), associated with altered circulating levels and adipose tissue mRNA expression proinflammatory cytokines interleukin-6 (IL-6) tumour necrosis factor (TNF)α, adiponectin. Proinflammatory adiponectin, which are secreted by tissue, regulate fat metabolism, insulin sensitivity cell apoptosis. We examined the direct effects individual antiretrovirals on lipid metabolism cytokine...
Side effects of antiretroviral treatment such as lipoatrophy have been mainly attributed to mitochondrial toxicity nucleoside reverse transcriptase inhibitors (NRTIs). We assessed whether uridine can abrogate the adverse NRTIs on adipocyte functions.3T3-F442A preadipocytes were exposed stavudine (d4T; 10 microM), zidovudine (ZDV; 1 zalcitabine (ddC; 0.2 microM) or didanosine (ddl; in absence presence 21 days prior and 7 after induction differentiation. Then, lipid accumulation (oil red...