A5047373721- Lipid metabolism and disorders
- Cancer, Lipids, and Metabolism
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Gut microbiota and health
- Atherosclerosis and Cardiovascular Diseases
- Peroxisome Proliferator-Activated Receptors
- Cholesterol and Lipid Metabolism
- Immune cells in cancer
- Liver Disease Diagnosis and Treatment
- Drug Transport and Resistance Mechanisms
- Immune Response and Inflammation
- Diet and metabolism studies
- Systemic Lupus Erythematosus Research
- Adipokines, Inflammation, and Metabolic Diseases
- Rheumatoid Arthritis Research and Therapies
- Cardiovascular Disease and Adiposity
- Cardiovascular Function and Risk Factors
- Tryptophan and brain disorders
- Diabetes and associated disorders
- Inflammatory mediators and NSAID effects
- Cell Adhesion Molecules Research
- Hepatitis B Virus Studies
- Glycosylation and Glycoproteins Research
- MicroRNA in disease regulation
- Lipid metabolism and biosynthesis
Amsterdam University Medical Centers
2019-2024
University of Amsterdam
2011-2024
University Medical Center
2019
University Hospital and Clinics
2019
Amsterdam UMC Location Vrije Universiteit Amsterdam
2019
Amsterdam UMC Location University of Amsterdam
2003-2018
Leiden University Medical Center
2018
Institute of Experimental Medicine
2005
Center for Vascular Biology Research
2001
Bariatric surgery improves glucose metabolism. Recent data suggest that faecal microbiota transplantation (FMT) using faeces from postbariatric diet-induced obese mice in germ-free metabolism and intestinal homeostasis. We here investigated whether allogenic FMT post-Roux-en-Y gastric bypass donors (RYGB-D) compared with metabolic syndrome (METS-D) has short-term effects on metabolism, transit time adipose tissue inflammation treatment-naïve, obese, insulin-resistant male subjects.Subjects...
Objective Environmental factors driving the development of type 1 diabetes (T1D) are still largely unknown. Both animal and human studies have shown an association between altered fecal microbiota composition, impaired production short-chain fatty acids (SCFA) T1D onset. However, observational evidence on SCFA oral in adults with longstanding vs healthy controls (HC) is lacking. Research design methods We included 53 patients without complications or medication 50 HC matched for age, sex...
Preliminary evidence from animal and human studies shows that gut microbiota composition levels of microbiota-derived metabolites, including short-chain fatty acids (SCFAs), are associated with blood pressure (BP). We hypothesized faecal derived metabolites may be differently BP across ethnic groups.We included 4672 subjects (mean age 49.8 ± 11.7 years, 52% women) six different groups participating in the HEalthy Life In an Urban Setting (HELIUS) study. The was profiled using 16S rRNA gene...
Liver regeneration in response to various forms of liver injury is a complex process, which ultimately results restoration the original mass and function. Because underlying mechanisms that initiate this are still incompletely defined, study was aimed identify novel factors. genes were up-regulated 6 h after 70% hepatectomy (PHx) rat selected by cDNA subtractive hybridization. Besides known associated with cell proliferation, several isolated. The gene most further studied. Its mRNA showed...
Lipopolysaccharide (LPS), the major glycolipid component of gram-negative bacterial outer membranes, is a potent endotoxin responsible for pathophysiological symptoms characteristic infection. The observation that majority LPS found in association with plasma lipoproteins has prompted suggestion sequestering by lipid particles may form an integral part humoral detoxification mechanism. Previous studies on biological properties isolated used differential ultracentrifugation to separate...
Abstract Plasma lipoproteins, such as high‐density lipoprotein (HDL), can serve carriers for a wide range of proteins that are involved in processes lipid metabolism, thrombosis, inflammation and atherosclerosis. The identification HDL‐associated is essential with regards to understanding these at the molecular level. In this study, combination proteomic approaches including 1‐DE 2‐DE MALDI‐TOF, isotope‐coded affinity tag Western blot analysis were employed identify associated human HDL. To...
Rationale: COMMD (copper metabolism MURR1 domain)-containing proteins are a part of the CCC (COMMD–CCDC22 [coiled-coil domain containing 22]–CCDC93 93]) complex facilitating endosomal trafficking cell surface receptors. Hepatic COMMD1 inactivation decreases CCDC22 and CCDC93 protein levels, impairs recycling LDLR (low-density lipoprotein receptor), increases plasma low-density cholesterol levels in mice. However, whether any other members function similarly as perturbation promotes...
Modulation of hematopoietic stem and progenitor cells (HSPCs) determines immune cell function. In this study, we investigated how hypercholesterolemia affects HSPC biology atherosclerosis. Hypercholesterolemia induced loss quiescence, characterized by increased proliferation expression cyclin B1, C1, D1, a decreased Rb, resulting in 3.6- fold increase the number HSPCs hypercholesterolemic Ldlr-/- mice. Competitive bone marrow (BM) transplantations showed that BM microenvironment activates...
Lipopolysaccharide (LPS), the major outer membrane component of gram-negative bacteria, is a potent endotoxin that triggers cytokine-mediated systemic inflammatory responses in host. Plasma lipoproteins are capable LPS sequestration, thereby attenuating host response to infection, but ensuing dyslipidemia severely compromises this defense mechanism. We have recently reported Escherichia coli J5 and Re595 chemotypes contain relatively short O-antigen polysaccharide side chains efficiently...
Abstract Objective Cardiovascular mortality is increased in ankylosing spondylitis (AS), and inflammation plays an important role. Inflammation deteriorates the lipid profile alters high‐density lipoprotein cholesterol (HDL‐c) composition, reflected by concentrations of serum amyloid A (SAA) within particle. Anti–tumor necrosis factor (anti‐TNF) treatment may improve these parameters. We therefore undertook present study to investigate effects etanercept on HDL composition AS. Methods In 92...
Obesity is associated with chronic low-grade inflammation, characterized by leukocytosis and inflammation in the adipose tissue. Continuous activation of immune system a stressor for hematopoietic stem progenitor cells (HSPCs) bone marrow (BM). Here we studied how diet-induced obesity (DIO) affects HSPC population dynamics BM. Eight groups age-matched C57Bl/6 mice received high-fat diet (45% kilocalories from fat) ranging 1 d up to 18 wk. The obesogenic caused decreased proliferation...
Airway infection with influenza virus induces local expression of the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO), which has been shown to enhance inflammatory mediator responses in vitro. Because secondary pneumococcal infections occurring shortly after recovery from are associated enhanced responses, we hypothesized that IDO activity contributes response bacterial challenges mice previously infected virus.On day 14 (with strain A/PR/8/34), C57Bl/6 were intranasally...
Peroxisome proliferator-activated receptor delta (PPARdelta) is involved in regulation of energy homeostasis. Activation PPARdelta markedly increases fecal neutral sterol secretion, the last step reverse cholesterol transport. This phenomenon can neither be explained by increased hepatobiliary nor reduced absorption. To test hypothesis that activation leads to stimulation transintestinal efflux (TICE), we quantified it intestine perfusions FVB mice treated with agonist GW610742. exclude...
6-phosphofructo-2-kinase/fructose-2,6-biphosphatase (PFKFB)3-mediated glycolysis is pivotal in driving macrophage- and endothelial cell activation thereby inflammation. Once activated, these cells play a crucial role the progression of atherosclerosis. Here, we analyzed expression PFKFB3 human atherosclerotic lesions investigated therapeutic potential pharmacological inhibition experimental atherosclerosis by using glycolytic inhibitor PFK158.PFKFB3 was higher vulnerable atheromatous carotid...
Abstract Aims CD40 and its ligand, CD40L, play a critical role in driving atherosclerotic plaque development. Disrupted CD40-signalling reduces experimental atherosclerosis induces favourable stable phenotype. We recently showed that small molecule-based inhibition of CD40-tumour necrosis factor receptor associated factor-6 interactions attenuates hyperlipidaemic mice via macrophage-driven mechanisms. The present study aims to detail the function myeloid using myeloid-specific CD40-deficient...
Lipopolysaccharide (LPS), the major glycolipid component of Gram-negative bacterial outer membranes, is a potent endotoxin responsible for many directly or indirectly induced symptoms infection. Lipoproteins (in particular, high-density lipoproteins) sequester LPS, thereby acting as humoral detoxification mechanism.Differences in lipoprotein composition human plasma and lymph control patient group (n = 5) without systemic inflammatory response syndrome (non-SIRS/MOF) patients with SIRS...
The importance of protein glycosylation in regulating lipid metabolism is becoming increasingly apparent. We set out to further investigate this by studying patients with type I congenital disorders (CDGs) defective N-glycosylation.We studied 29 the 2 most prevalent types CDG, ALG6 (asparagine-linked 6)-deficiency CDG and PMM2 (phosphomannomutase 2)-deficiency 23 first- second-degree relatives a heterozygous mutation measured plasma cholesterol levels. Low-density lipoprotein (LDL) was 3...
Elevated nonfasting TG-rich lipoprotein levels are a risk factor for CVD. To further evaluate the relevance of LDL-receptor (LDLr) pathway and heparan sulfate proteoglycans (HSPGs) in TG homeostasis, we analyzed fasting postprandial mice bearing combined heterozygous mutations both Exostosin (Ext) 1 Ldlr, subjects with hereditary multiple exostosis (HME) due to loss-of-function mutation EXT1 or EXT2 (N = 13), patients LDLR [familial hypercholesterolemia (FH)] SNPs major HSPG-related genes (n...
Background and aimsAtherosclerosis is a lipid-driven chronic inflammatory disorder of the arteries, monocytes macrophages play central role in this process. Within atherosclerotic lesion, can scavenge modified lipids become so-called foam cells. We previously reported that epigenetic enzyme Kdm6b (also known as Jmjd3) controls pro-fibrotic transcriptional profile peritoneal Given importance these cells atherosclerosis, we now studied effect myeloid on disease progression.MethodsBone marrow...
Recently, novel inborn errors of metabolism were identified because mutations in V-ATPase assembly factors TMEM199 and CCDC115. Patients are characterized by generalized protein glycosylation defects, hypercholesterolemia, fatty liver disease. Here, we set out to characterize the lipid phenotype human plasma, cell models, a mouse model.Patients with CCDC115 displayed hyperlipidemia, increased levels lipoproteins very low density lipoprotein range. HepG2 hepatoma cells, which expression was...