document

Sex differences in skeletal muscle-aging trajectory: same processes, but with a different ranking

de Jong, J.C.B.C. (author), Attema, B.J. (author), van der Hoek, M.D. (author), Verschuren, L. (author), Caspers, M.P.M. (author), Kleemann, R. (author), van der Leij, F.R. (author), van den Hoek, A.M. (author), Nieuwenhuizen, A.G. (author), Keijer, J. (author)

Sex differences in muscle aging are poorly understood, but could be crucial for the optimization of sarcopenia-related interventions. To gain insight into potential sex differences in muscle aging, we recruited young (23 ± 2 years, 13 males and 13 females) and old (80 ± 3.5 years, 28 males and 26 females) participants. Males and females in both...

article 2023

document

Translational characterization of the temporal dynamics of metabolic dysfunctions in liver, adipose tissue and the gut during diet-induced NASH development in Ldlr-/-.Leiden mice

Gart, E. (author), van Duyvenvoorde, W. (author), Snabel, J. (author), de Ruiter, C. (author), Attema, J. (author), Caspers, M.P.M. (author), Lek, S. (author), van Heuven, B.J. (author), Speksnijder, A.G.C.L. (author), Giera, M. (author), Menke, A. (author), Salic, K. (author), Bence, K.K. (author), Tesz, G.J. (author), Keijzer, J. (author), Kleemann, R. (author), Morrison, M.C. (author)

Background: NAFLD progression, from steatosis to inflammation and fibrosis, results from an interplay of intra- and extrahepatic mechanisms. Disease drivers likely include signals from white adipose tissue (WAT) and gut. However, the temporal dynamics of disease development remain poorly understood. Methods: High-fat-diet (HFD)-fed Ldlr-/-...

article 2023

document

Sex difference in skeletal muscle-ageing trajectory: same processes, but with different magnitudes: poster

Jong, J.C.B.C. (author), Attema, B.J. (author), van der Hoek, M.D. (author), Verschuren, L. (author), Caspers, M.P.M. (author), Kleemann, R. (author), van der Leij, F.R. (author), van den Hoek, A.M. (author), Nieuwenhuizen1, A.G. (author), Keijer, J. (author)

Sex differences in muscle‐ageing are incompletely understood and could be crucial for the optimalisation of sarcopenia‐related interventions. • Therefore, we performed an observational trial to gain insight in potential sex differences in processes involved in human muscle‐ageing.

public lecture 2022

document

An altered microbiota pattern precedes Type 2 diabetes mellitus development: From the CORDIOPREV study

Vals-Delgado, C. (author), Alcala-Diaz, J.F. (author), Molina-Abril, H. (author), Roncero-Ramos, I. (author), Caspers, M.P.M. (author), Schuren, F.H.J. (author), van den Broek, T.J. (author), Luque, R. (author), Perez-Martinez, P. (author), Katsiki, N. (author), Delgado-Lista, J. (author), Ordovas, J.M. (author), van Ommen, B. (author), Camargo, A (author), Lopez-Miranda, J. (author)

Introduction: A distinctive gut microbiome have been linked to type 2 diabetes mellitus (T2DM). Objectives: We aimed to evaluate whether gut microbiota composition, in addition to clinical biomarkers, could improve the prediction of new incident cases of diabetes in patients with coronary heart disease. Methods: All the patients from the...

article 2022

document

The Human Milk Oligosaccharide 2'-Fucosyllactose Alleviates Liver Steatosis, ER Stress and Insulin Resistance by Reducing Hepatic Diacylglycerols and Improved Gut Permeability in Obese Ldlr-/-.Leiden Mice

Gart, E. (author), Salic, K. (author), Morrison, M.C. (author), Giera, M. (author), Attema, J. (author), de Ruiter, C. (author), Caspers, M.P.M. (author), Schuren, F. (author), Bobeldijk-Pastorova, I. (author), Heer, M. (author), Qin, Y. (author), Kleemann, R. (author)

Non-alcoholic fatty liver disease (NAFLD) is a complex multifactorial disorder that is associated with gut dysbiosis, enhanced gut permeability, adiposity and insulin resistance. Prebiotics such as human milk oligosaccharide 2'-fucosyllactose are thought to primarily improve gut health and it is uncertain whether they would affect more distant...

article 2022

document

Unraveling the Transcriptional Dynamics of NASH Pathogenesis Affecting Atherosclerosis

van den Hoek, A.M. (author), Özsezen, S. (author), Caspers, M.P.M. (author), van Koppen, A. (author), Hanemaaijer, R. (author), Verschuren, L. (author)

The prevalence of non-alcoholic steatohepatitis (NASH) is rapidly increasing and associated with cardiovascular disease (CVD), the major cause of mortality in NASH patients. Although sharing common risk factors, the mechanisms by which NASH may directly contribute to the development to CVD remain poorly understood. The aim of this study is to...

article 2022

document

Intervention with isoleucine or valine corrects hyperinsulinemia and reduces intrahepatic diacylglycerols, liver steatosis, and inflammation in Ldlr-/-.Leiden mice with manifest obesity-associated NASH

Gart, E. (author), van Duyvenvoorde, W. (author), Caspers, M.P.M. (author), van Trigt, N. (author), Snabel, J. (author), Menke, A. (author), Keijer, J. (author), Salic, K. (author), Morrison, M.C. (author), Kleemann, R. (author)

Non-alcoholic steatohepatitis (NASH) is associated with a disturbed metabolism in liver, insulin resistance, and excessive accumulation of ectopic fat. Branched-chain amino acids (BCAAs) may beneficially modulate hepatic lipids, however, it remains unclear whether individual BCAAs can attenuate already established NASH and associated oxidative...

article 2022

document

Predicting the allergenicity of legume proteins using a PBMC gene expression assay

Smits, M. (author), Meijerink, M. (author), Le, T.M. (author), Knulst, A. (author), de Jong, A. (author), Caspers, M.P.M. (author), Lima, E.S. (author), Babe, L. (author), Ladics, G. (author), McClain, S. (author), Houben, G.F. (author), Verhoeckx, K. (author)

Background: Food proteins differ in their allergenic potential. Currently, there is no predictive and validated bio-assay to evaluate the allergenicity of novel food proteins. The objective of this study was to investigate the potential of a human peripheral blood mononuclear cell (PBMC) gene expression assay to identify biomarkers to predict...

article 2021

document

A Novel Personalized Systems Nutrition Program Improves Di-2 etary Patterns, Lifestyle Behaviors and Health-Related Out-3 comes: Results from the Habit Study

de Hoogh, I.M. (author), Winters, B.L. (author), Nieman, K.M. (author), Bijlsma, S. (author), Krone, T. (author), van den Broek, T.J. (author), Anderson, B.D. (author), Caspers, M.P.M. (author), Anthony, J.C. (author), Wopereis, S. (author)

Personalized nutrition may be more effective in changing lifestyle behaviors compared to population-based guidelines. This single-arm exploratory study evaluated the impact of a 10-week personalized systems nutrition (PSN) program on lifestyle behavior and health outcomes. Healthy men and women (n = 82) completed the trial. Individuals were...

article 2021

document

Butyrate Protects against Diet-Induced NASH and Liver Fibrosis and Suppresses Specific Non-Canonical TGF-β Signaling Pathways in Human Hepatic Stellate Cells

Gart, E. (author), van Duyvenvoorde, W. (author), Toet, K. (author), Caspers, M.P.M. (author), Verschuren, L. (author), Nielsen, M.J. (author), Leeming, D.J. (author), Lima, E.S. (author), Menke, A. (author), Hanemaaijer, R. (author), Keijer, J. (author), Salic, K. (author), Kleemann, R. (author), Morrison, M.C. (author)

In obesity-associated non-alcoholic steatohepatitis (NASH), persistent hepatocellular damage and inflammation are key drivers of fibrosis, which is the main determinant of NASH-associated mortality. The short-chain fatty acid butyrate can exert metabolic improvements and anti-inflammatory activities in NASH. However, its effects on NASH...

article 2021

document

Mechanism-Based Biomarker Prediction for Low-Grade Inflammation in Liver and Adipose Tissue

van Bilsen, J.H.M. (author), van den Brink, W. (author), van den Hoek, A.M. (author), Dulos, R. (author), Caspers, M.P.M. (author), Kleeman, R. (author), Wopereis, S. (author), Verschuren, L. (author)

Metabolic disorders, such as obesity and type 2 diabetes have a large impact on global health, especially in industrialized countries. Tissue-specific chronic low-grade inflammation is a key contributor to complications in metabolic disorders. To support therapeutic approaches to these complications, it is crucial to gain a deeper understanding...

article 2021

document

Beneficial effects of elafibranor on NASH in E3L.CETP mice and differences between mice and men

van den Hoek, A.M. (author), Verschuren, L. (author), Caspers, M.P.M. (author), Worms, N. (author), Menke, A.L. (author), Princen, H.M.G. (author)

Non-alcoholic steatohepatitis (NASH) is the most rapidly growing liver disease that is nevertheless without approved pharmacological treatment. Despite great effort in developing novel NASH therapeutics, many have failed in clinical trials. This has raised questions on the adequacy of preclinical models. Elafibranor is one of the drugs currently...

article 2021

document

Diet and exercise reduce pre-existing NASH and fibrosis and have additional beneficial effects on the vasculature, adipose tissue and skeletal muscle via organ-crosstalk

van den Hoek, A.M. (author), de Jong, J.C.B.C. (author), Worms, N. (author), van Nieuwkoop, A. (author), Voskuilen, M. (author), Menke, A.L. (author), Lek, S. (author), Caspers, M.P.M. (author), Verschuren, L. (author), Kleemann, R. (author)

Background. Non-alcoholic steatohepatitis (NASH) has become one of the most common liver diseases and is still without approved pharmacotherapy. Lifestyle interventions using exercise and diet change remain the current treatment of choice and even a small weight loss (5–7%) can already have a beneficial effect on NASH. However, the underlying...

article 2021

document

A Translational Mouse Model for NASH with Advanced Fibrosis and Atherosclerosis Expressing Key Pathways of Human Pathology

van den Hoek, A.M. (author), Verschuren, L. (author), Worms, N. (author), van Nieuwkoop, A. (author), de Ruiter, C. (author), Attema, J. (author), Menke, A.L. (author), Caspers, M.P.M. (author), Radhakrishnan, S. (author), Salic, K. (author), Kleemann, R. (author)

Non-alcoholic steatohepatitis (NASH) is a fast-growing liver disorder that is associated with an increased incidence of cardiovascular disease and type 2 diabetes. Animal models adequately mimicking this condition are scarce. We herein investigate whether Ldlr−/−. Leiden mice on different high-fat diets represent a suitable NASH model. Ldlr−/−....

article 2020

document

The BCR-ABL1 Inhibitors Imatinib and Ponatinib Decrease Plasma Cholesterol and Atherosclerosis, and Nilotinib and Ponatinib Activate Coagulation in a Translational Mouse Model

Pouwer, M.G. (author), Pieterman, E.J. (author), Verschuren, L. (author), Caspers, M.P.M. (author), Kluft, C. (author), Garcia, R.A. (author), Aman, J. (author), Jukema, J.W. (author), Princen, H.M.G. (author)

Treatment with the second and third generation BCR-ABL1 tyrosine kinase inhibitors (TKIs) increases cardiovascular risk in chronic myeloid leukemia (CML) patients. We investigated the vascular adverse effects of three generations of TKIs in a translational model for atherosclerosis, the APOE*3Leiden.CETP mouse. Mice were treated for sixteen...

article 2018

document

Obeticholic Acid Modulates Serum Metabolites and Gene Signatures Characteristic of Human NASH and Attenuates Inflammation and Fibrosis Progression in Ldlr-/-.Leiden Mice

Morrison, M.C. (author), Verschuren, L. (author), Salic, K. (author), Verhij, J. (author), Menke, A. (author), Wielinga, P.Y. (author), Iruarrizaga-Lejarretts, M. (author), Gole, L. (author), Yu, W.M. (author), Turner, S. (author), Caspers, M.P.M. (author), Martinez-Arranz, I. (author), Pieterman, E. (author), Stoop, R. (author), van Koppen, A. (author), van den Hoek, A.M. (author), Mato, J.M. (author), Hanemaaijer, R. (author), Alonso, C. (author), Kleemann, R. (author)

Concerns have been raised about whether preclinical models sufficiently mimic molecular disease processes observed in nonalcoholic steatohepatitis (NASH) patients, bringing into question their translational value in studies of therapeutic interventions in the process of NASH/fibrosis. We investigated the representation of molecular disease...

article 2018

document

Short communication Growth of dairy isolates of Geobacillus thermoglucosidans in skim milk depends on lactose degradation products supplied by Anoxybacillus flavithermus as secondary species

Zhao, Y. (author), Kumar, M. (author), Caspers, M.P.M. (author), Nierop Groot, M.N. (author), van der Vossen, J.M.B.M. (author), Abee, T. (author)

Thermophilic bacilli such as Anoxybacillus and Geobacillus are important contaminants in dairy powder products. Remarkably, one of the common contaminants, Geobacillus thermoglucosidans, showed poor growth in skim milk, whereas significant growth of G. thermoglucosidans was observed in the presence of an Anoxybacillus flavithermus dairy isolate....

article 2018

document

Uncovering a Predictive Molecular Signature for the Onset of NASH-Related Fibrosis in a Translational NASH Mouse Model

van Koppen, A. (author), Verschuren, L. (author), van den Hoek, A.M. (author), Verheij, J. (author), Morrison, M.C. (author), Li, K. (author), Nagabukuro, H. (author), Costessi, A. (author), Caspers, M.P.M. (author), van den Broek, T.J. (author), Sagartz, J. (author), Kluft, C. (author), Beysen, C. (author), Emson, C. (author), van Gool, A.J. (author), Goldschmeding, R. (author), Stoop, R. (author), Bobeldijk-Pastorova, I. (author), Turner, S.M. (author), Hanauer, G. (author), Hanemaaijer, R. (author)

Background & Aims: The incidence of nonalcoholic steatohepatitis (NASH) is increasing. The pathophysiological mechanisms of NASH and the sequence of events leading to hepatic fibrosis are incompletely understood. The aim of this study was to gain insight into the dynamics of key molecular processes involved in NASH and to rank early markers for...

article 2017

document

Molecular assessment of bacterial vaginosis by Lactobacillus abundance and species diversity

Dols, J.A.M. (author), Molenaar, D. (author), van der Helm, J.J. (author), Caspers, M.P.M. (author), de Kat Angelino-Bart, A. (author), Schuren, F.H.J. (author), Speksnijder, A.G.C.L. (author), Westerhoff, H.V. (author), Richardus, J.H. (author), Boon, M.E. (author), Reid, G. (author), de Vries, H.J.C. (author), Kort, R. (author)

Background: To date, women are most often diagnosed with bacterial vaginosis (BV) using microscopy based Nugent scoring or Amsel criteria. However, the accuracy is less than optimal. The aim of the present study was to confirm the identity of known BV-associated composition profiles and evaluate indicators for BV using three molecular methods....

article 2016

document

Draft genome sequences of four thermophilic spore formers isolated from a dairyprocessing environment

Caspers, M.P.M. (author), Boekhorst, J. (author), Jong, A. (author), Kort, R. (author), Groot, M.N. (author), Abee, T. (author)

article 2016