A5063674598- Liver Disease Diagnosis and Treatment
- Adipose Tissue and Metabolism
- Diet and metabolism studies
- Adipokines, Inflammation, and Metabolic Diseases
- Macrophage Migration Inhibitory Factor
- Nuclear Receptors and Signaling
- Diet, Metabolism, and Disease
- Atherosclerosis and Cardiovascular Diseases
- Lipoproteins and Cardiovascular Health
- Peroxisome Proliferator-Activated Receptors
- Cholesterol and Lipid Metabolism
- Fatty Acid Research and Health
- Cancer, Lipids, and Metabolism
- Lipid metabolism and disorders
- Metabolomics and Mass Spectrometry Studies
- Cardiovascular Disease and Adiposity
- Regulation of Appetite and Obesity
- Nutrition and Health in Aging
- Endoplasmic Reticulum Stress and Disease
- Computational Drug Discovery Methods
- Aortic aneurysm repair treatments
- Spectroscopy Techniques in Biomedical and Chemical Research
- Spectroscopy and Chemometric Analyses
- Nutrition, Genetics, and Disease
- Gut microbiota and health
Netherlands Organisation for Applied Scientific Research
2016-2025
Netherlands Consortium for Healthy Ageing
2024
Boehringer Ingelheim (Germany)
2023
Leiden University Medical Center
2009-2022
Wageningen University & Research
2015-2022
Queen Mary University of London
2022
Rijnstate Hospital
2022
Radboud University Nijmegen
2020-2022
Radboud University Medical Center
2020-2022
University Medical Center
2022
Development of non-alcoholic fatty liver disease (NAFLD) is linked to obesity, adipose tissue inflammation, and gut dysfunction, all which depend on diet. So far, studies have mainly focused diet-related fecal microbiota changes, but other compartments may be more informative host health. We present a first systematic analysis changes in the ileum colon using multiple diets investigating both mucosal samples. Ldlr−/−.Leiden mice received one three different energy-dense (ED)-diets (n =...
Background and aims The recently developed histological scoring system for non-alcoholic fatty liver disease (NAFLD) by the NASH Clinical Research Network (NASH-CRN) has been widely used in clinical settings, but is increasingly employed preclinical research as well. However, it not systematically analyzed whether human can directly be converted to rodent models. To analyze this, we compared NAFLD pathology, using biopsies, with pathology of several mouse Based upon features pertaining...
Aging | doi:10.18632/aging.100738. Roel A van der Heijden, Fareeba Sheedfar, Martine C Morrison, Pascal PH Hommelberg, Danny Kor, Niels J Kloosterhuis, Nanda Gruben, Sameh Youssef, Alain de Bruin, Marten H Hofker, Robert Kleemann, Debby PY Koonen, Peter Heeringa
The fasting-induced adipose factor (FIAF, ANGPTL4, PGAR, HFARP) was previously identified as a novel adipocytokine that up-regulated by fasting, peroxisome proliferator-activated receptor agonists, and hypoxia. To further characterize FIAF, we studied regulation of FIAF mRNA protein in liver cell lines well human mouse plasma. Expression alpha (PPARalpha) PPARbeta/delta agonists rat hepatoma PPARgamma adipocytes. Transactivation, chromatin immunoprecipitation, gel shift experiments...
Background — Atherosclerosis is a chronic inflammatory response of the arterial wall to injury. Macrophage migration inhibitory factor (MIF), cytokine with potent functions, was thus considered be important in atherosclerotic lesion evolution. Methods and Results We studied presence distribution MIF immunoreactivity (MIF-IR) mRNA internal mammary arteries normal histology plaques different stages human atherosclerosis. To address potential role for coactivator Jab1 as cellular mediator...
Background— Doxycycline has been shown to effectively inhibit aneurysm formation in animal models of abdominal aortic aneurysm. Although this effect is ascribed matrix metalloproteinase-9 inhibition, such an unclear human studies. We reevaluated the doxycycline on wall protease content a clinical trial and found that selectively reduces neutrophil-derived proteases. thus hypothesized acts through vascular inflammation. Methods Results— Sixty patients scheduled for elective open aneurysmal...
Abstract Background Increased dietary cholesterol intake is associated with atherosclerosis. Atherosclerosis development requires a lipid and an inflammatory component. It unclear where how the component develops. To assess role of liver in evolution inflammation, we treated ApoE*3Leiden mice cholesterol-free (Con), low (LC; 0.25%) high (HC; 1%) diets, scored early atherosclerosis profiled (patho)physiological state using novel whole-genome metabolome technologies. Results Whereas Con diet...
The peroxisome proliferator-activated receptor alpha (PPARalpha), which is highly expressed in liver, plays key roles lipid metabolism and inflammation. Interleukin-6 (IL-6) the principal inducer of acute phase response (APR) gene expression. In present study, we demonstrate that chronic treatment with PPARalpha agonist fenofibrate fully prevents IL-6-induced APR expression wild-type but not PPARalpha-deficient mice. positive genes fibrinogen-alpha, -beta, -gamma, haptoglobulin, serum...
Background The sequence of events leading to the development insulin resistance (IR) as well underlying pathophysiological mechanisms are incompletely understood. As reductionist approaches have been largely unsuccessful in providing an understanding pathogenesis IR, there is a need for integrative, time-resolved approach elucidate disease. Methodology/Principal Findings Male ApoE3Leiden transgenic mice exhibiting humanized lipid metabolism were fed high-fat diet (HFD) 0, 1, 6, 9, or 12...
Chronic inflammation in white adipose tissue (WAT) is positively associated with obesity, insulin resistance (IR) and the development of type 2 diabetes. The proinflammatory cytokine MIF (macrophage migration inhibitory factor) an essential, upstream component inflammatory cascade. This study examines whether required for IR, glucose intolerance, atherosclerosis LDL receptor-deficient (Ldlr −/− ) mouse model disease. Ldlr mice develop IR intolerance within 15 weeks, whereas Mif littermates...
We introduce the metabolomics and proteomics based Postprandial Challenge Test (PCT) to quantify postprandial response of multiple metabolic processes in humans a standardized manner. The PCT comprised consumption 500 ml dairy shake containing respectively 59, 30 12 energy percent lipids, carbohydrates protein. During 6 h time course after 145 plasma metabolites, 79 proteins 7 clinical chemistry parameters were quantified. Multiple related metabolism, oxidation inflammation reacted PCT, as...
Statins are thought to reduce vascular inflammation through lipid independent mechanisms. Evaluation of such an effect in atherosclerotic disease is complicated by simultaneous effects on metabolism. Abdominal aortic aneurysms (AAA) part the spectrum diseases. Unlike occlusive disease, AAA not driven, thus allowing direct evaluation putative anti-inflammatory effects. The potency increasing doses (0, 20 or 40 mg/day) simvastatin atorvastatin was evaluated 63 patients that were at least 6...
Besides LDL-cholesterol, local vascular inflammation plays a key role in atherogenesis. Efficient therapies to treat the inflammatory component of disease have not been established. The discovery specialized inflammation-resolving mediators, such as resolvins may provide new opportunities for treatment. This study examines whether ω-3 fatty acid eicosapentaenoic acid-derived resolvin E1 (RvE1), can reduce atherosclerosis, when administered alone or combination with cholesterol-lowering...