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van Son, K.C. (author), Verschuren, L. (author), Hanemaaijer, R. (author), Reeves, H. (author), Takkenberg, R.B. (author), Drenth, J.P.H. (author), Tushuizen, M.E. (author), Holleboom, A.G. (author)Hepatocellular carcinoma (HCC) in the setting of non-alcoholic fatty liver disease (NAFLD)-related cirrhosis and even in the pre-cirrhotic state is increasing in incidence. NAFLD-related HCC has a poor clinical outcome as it is often advanced at diagnosis due to late diagnosis and systemic treatment response is poor due to reduced immune...article 2023
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Morrison, M.C. (author), Egelandsdal, B. (author), Harvei, S. (author), Rocha, S.D.C. (author), Pieterman, E.J. (author), Kleemann, R. (author), Carlsen, H. (author)Cardiovascular disease (CVD) is closely associated with obesity through risk factors such as dyslipidemia and chronic low-grade inflammation, which may be affected by diet. Dietary fats have been extensively studied in relation to CVD risk, however these studies have not always yielded consistent results, most likely due to lack in control of...article 2023
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Seidel, F. (author), Kleemann, R. (author), van Duyvenvoorde, W. (author), van Trigt, N. (author), Keijzer, N. (author), van der Kooij, S. (author), van Kooten, C. (author), Verschuren, L. (author), Menke, A. (author), Kiliaan, A.J. (author), Winter, J. (author), Hughes, T.R. (author), Morgan, P. (author), Baas, F. (author), Fluiter, K. (author), Morrison, M.C. (author)Background: Chronic inflammation is an important driver in the progression of non-alcoholic steatohepatitis (NASH) and atherosclerosis. The complement system, one of the first lines of defense in innate immunity, has been implicated in both diseases. However, the potential therapeutic value of complement inhibition in the ongoing disease remains...article 2022
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Warmink, K. (author), Kozijn, A.E. (author), Bobeldijk, I. (author), Stoop, R. (author), Weinans, H. (author), Korthagen, N.M. (author)Objective. Obesity is one of the greatest risk factors for osteoarthritis (OA) and evidence is accumulating that inflammatory mediators and innate immunity play an important role. The infrapatellar fat pad (IPFP) could be a potential local source of inflammatory mediators in the knee. Here, we combine surgical joint damage with high-fat feeding...article 2020
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Pouwer, M.G. (author), Pieterman, E.J. (author), Worms, N. (author), Keijzer, N. (author), Jukema, J.W. (author), Gromada, J. (author), Gusarova, V. (author), Princen, H.M.G. (author)Atherosclerosis-related cardiovascular disease causes nearly 20 million deaths annually. Most patients are treated after plaques develop, so therapies must regress existing lesions. Current therapies reduce plaque volume, but targeting all apoB-containing lipoproteins with intensive combinations that include alirocumab or evinacumab-monoclonal...article 2020
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Kozijn, A.E. (author)This thesis aimed to investigate how metabolic overload contributes to the pathophysiology of knee OA. We explored the role of these independent yet intertwined processes using state-of-the-art lipidomic and cellular approaches in mouse models of diet-induced OA. Chapter 2 presents an overview of twelve preclinical studies in which mice received...doctoral thesis 2020
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Hardtner, C. (author), Kornemann, J. (author), Krebs, K. (author), Ehlert, C.A. (author), Jander, A. (author), Zou, J. (author), Christopher, (author), Starz, C. (author), Rauterberg, S. (author), Sharipova, D. (author), Dufner, B. (author), Hoppe, N. (author), Dederichs, T.S. (author), Willecke, F. (author), Stachon, p. (author), Heidt, T. (author), Wolf, D. (author), von zur Muhlen, C. (author), Madl, J. (author), Kohl, P. (author), Kaeser, R. (author), Boettler, T. (author), Pieterman, E.J. (author), Princen, H.M.G. (author), Ho-Tin-Noe, B. (author), Swirski, F.K. (author), Robbins, C.S. (author), Bode, C. (author), Zirlik, A. (author), Hilgendorf, I. (author)Statins induce plaque regression characterized by reduced macrophage content in humans, but the underlying mechanisms remain speculative. Studying the translational APOE*3-Leiden.CETP mouse model with a humanized lipoprotein metabolism, we find that systemic cholesterol lowering by oral atorvastatin or dietary restriction inhibits monocyte...article 2020
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Tans, R. (author), van Diepen, J.A. (author), Bijlsma, S. (author), Verschuren, L. (author), Suppers, A. (author), Stienstra, R. (author), Wevers, R.A. (author), Tack, C.J. (author), Gloerich, J. (author), van Gool, A.J. (author)Background: Overweight and obesity can lead to adipose tissue inflammation, which causes insulin resistance and on the long-term type 2 diabetes mellitus (T2D). The inflammatory changes of obese-adipose tissue are characterized by macrophage infiltration and activation, but validated circulating biomarkers for adipose tissue inflammation for...article 2019
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Yakala, G.K. (author), Cabrera-Fuentes, H.A. (author), Crespo-Avilan, G.E. (author), Rattanasopa, C. (author), Burlacu, A. (author), George, B.L. (author), Anand, K. (author), Mayan, D.C. (author), Corliano, M. (author), Hernandez-Resendiz, S. (author), Wu, Z. (author), Schwerk, A.M.K. (author), Tan, A.L.J. (author), Trigueros-Motos, L. (author), Chevre, R. (author), Chua, T. (author), Kleemann, R. (author), Liehn, E.A. (author), Hausenloy, D.J. (author), Ghosh, S. (author), Singaraja, R.R. (author)Objective- Atherosclerotic coronary artery disease is the leading cause of death worldwide, and current treatment options are insufficient. Using systems-level network cluster analyses on a large coronary artery disease case-control cohort, we previously identified PCSK3 (proprotein convertase subtilisin/kexin family member 3; FURIN) as a member...article 2019
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Rusli, F. (author), Boekschoten, M.V. (author), Borelli, V. (author), Sun, C. (author), Lute, C. (author), Menke, A.L. (author), van den Heuvel, J. (author), Salvioli, S. (author), Franceschi, C. (author), Müller, M. (author), Steegenga, W.T. (author)Calorie restriction (CR) is a dietary regimen that supports healthy aging. In this study, we investigated the systemic and liver-specific responses caused by a diet switch to a medium-fat (MF) diet in 24-month-old lifelong, CR-exposed mice. This study aimed to increase the knowledge base on dietary alterations of gerontological relevance. Nine...article 2018
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Pelgrim, C.E. (author), Franx, B.A.A. (author), Snabel, J. (author), Kleemann, R. (author), Arnoldussen, I.A.C. (author), Kiliaan, A.J. (author)Adipose tissue (AT) has a modulating role in obesity-induced metabolic complications like type 2 diabetes mellitus (T2DM) via the production of so-called adipokines such as leptin, adiponectin, and resistin. The adipokines are believed to influence other tissues and to affect insulin resistance, liver function, and to increase the risk of T2DM....article 2017
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de Jong, A.J. (author), Klein-Wietinga, I.R. (author), Andersen, S.N. (author), Kwekkeboom, J.C. (author), Herb-van Toorn, L. (author), de Lange-Brokaar, B.J.E. (author), van Delft, D. (author), Garcia, J. (author), Wei, W. (author), van der Heide, H.J.L. (author), Bastiaanen-Jenniskens, Y.M. (author), van Osch, G.J.V.M. (author), Zuurmond, A.M. (author), Stojanovic-Susulic, V. (author), Nelissen, R.G. (author), Toes, R.E.M. (author), Kloppenburg, M. (author), Ioan-Facsinay, A. (author)Background. Obesity is associated with the development and progression of osteoarthritis (OA). Although the infrapatellar fat pad (IFP) could be involved in this association, due to its intracapsular localization in the knee joint, there is currently little known about the effect of obesity on the IFP. Therefore, we investigated cellular and...article 2017
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Morrison, M.C. (author), Kleemann, R. (author)Obesity is associated with a chronic low-grade inflammatory state that drives the -development of obesity-related co-morbidities such as insulin resistance/type 2 diabetes, non-alcoholic fatty liver disease (NAFLD), and cardiovascular disease. This metabolic inflammation is thought to originate in the adipose tissue, which becomes inflamed and...article 2015
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Wang, Y. (author), Parlevliet, E.T. (author), Geerling, J.J. (author), van der Tuin, S.J.L. (author), Zhang, H. (author), Bieghs, V. (author), Jawad, A.H.M. (author), Shiri-Sverdlov, R. (author), Bot, I. (author), de Jager, S.C.A. (author), Havekes, L.M. (author), Romijn, J.A. (author), Willems Van Dijk, K. (author), Rensen, P.C.N. (author)Background and Purpose The aetiology of inflammation in the liver and vessel wall, leading to non-alcoholic steatohepatitis (NASH) and atherosclerosis, respectively, shares common mechanisms including macrophage infiltration. To treat both disorders simultaneously, it is highly important to tackle the inflammatory status. Exendin-4, a glucagon...article 2014
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Harb, H. (author), van Tol, E.A.F. (author), Heine, H. (author), Braaksma, M. (author), Gross, G. (author), Overkamp, K. (author), Hennen, M. (author), Alrifai, M. (author), Conrad, M.L. (author), Renz, H. (author), Garn, H. (author)Background: Oral supplementation with probiotic bacteria can protect against the development of allergic and inflammatory diseases. Objective: The aim of this study was to investigate potential immunomodulatory and allergy-protective effects of processed Lactobacillus rhamnosus GG (LGG)-derived supernatants early in life in neonatal mice....article 2013
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Khedoe, P.P.S.J. (author), Wong, M.C. (author), Wagenaar, G.T.M. (author), Plomp, J.J. (author), van Eck, M. (author), Havekes, L.M. (author), Rensen, P.C.N. (author), Hiemstra, P.S. (author), Berbée, J.F.P. (author)Background: Chronic obstructive pulmonary disease (COPD) is characterized by pulmonary inflammation, airways obstruction and emphysema, and is a risk factor for cardiovascular disease (CVD). However, the contribution of these individual COPD components to this increased risk is unknown. Therefore, the aim of this study was to determine the...article 2013
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Georgiadi, A. (author), Wang, Y. (author), Stienstra, R. (author), Tjeerdema, N. (author), Janssen, A. (author), Stalenhoef, A. (author), van der Vliet, J.A. (author), de Roos, A. (author), Tamsma, J.T. (author), Smit, J.W. (author), Tan, N.S. (author), Müller, M. (author), Rensen, P.C. (author), Kersten, S. (author)Objective: Macrophage foam cells play a crucial role in several pathologies including multiple sclerosis, glomerulosclerosis, and atherosclerosis. Angiopoietin-like protein 4 (Angptl4) was previously shown to inhibit chyle-induced foam cell formation in mesenteric lymph nodes. Here we characterized the regulation of Angptl4 expression in...article 2013
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de Lange-Brokaar, B.J.E. (author), Ioan-Facsinay, A. (author), van Osch, G.J.V.M. (author), Zuurmond, A.-M. (author), Schoones, J. (author), Toes, R.E.M. (author), Huizinga, T.W.J. (author), Kloppenburg, M. (author)Objective: Although osteoarthritis (OA) is considered a non-inflammatory condition, it is widely accepted that synovial inflammation is a feature of OA. However, the role of immune cells and their cytokines in OA is largely unknown. This narrative systematic review summarizes the knowledge of inflammatory properties, immune cells and their...article 2012
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Mariman, R. (author), Kremer, S.H.A. (author), van Erk, M. (author), Lagerweij, T. (author), Koning, F. (author), Nagelkerken, L. (author)Background: Host-microbiota interactions in the intestinal mucosa play a major role in intestinal immune homeostasis and control the threshold of local inflammation. The aim of this study was to evaluate the efficacy of probiotics in the recurrent trinitrobenzene sulfonic acid (TNBS)-induced colitis model and gain more insight into protective...article 2012
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Li, Z. (author), Wang, Y. (author), van der Sluis, R.J. (author), van der Hoorn, J.W.A. (author), Princen, H.M.G. (author), van Eck, M. (author), van Berkel, T.J.C. (author), Rensen, P.C.N. (author), Hoekstra, M. (author)The anti-dyslipidemic drug niacin has recently been shown to reduce the hepatic expression and plasma levels of CETP. Since liver macrophages contribute to hepatic CETP expression, we investigated the role of macrophages in the CETP-lowering effect of niacin in mice. In vitro studies showed that niacin does not directly attenuate CETP expression...article 2012