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Lipid ratios representing SCD1, FADS1, and FADS2 activities as candidate biomarkers of early growth and adiposity

Olga, L. (author), van Diepen, J.A. (author), Bobeldijk-Pastorova, I. (author), Gross, G. (author), Prentice, S.M. (author), Snowden, S.G. (author), Furse, S. (author), Kooistra, T. (author), Hughes, I.A. (author), Schoemaker, M.H. (author), van Tol, E.A.F. (author), van Duyvenvoorde, W. (author), Wielinga, P.Y. (author), Ong, K.K. (author), Dunger, D.B. (author), Kleemann, R. (author), Koulman, A. (author)

Background: Altered lipid metabolism in early life has been associated with subsequent weight gain and predicting this could aid in obesity prevention and risk management. Here, a lipidomic approach was used to identify circulating markers for future obesity risk in translational murine models and validate in a human infant cohort. Methods:...

article 2021

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Combined Treatment with L-Carnitine and Nicotinamide Riboside Improves Hepatic Metabolism and Attenuates Obesity and Liver Steatosis

Salic, K. (author), Gart, E. (author), Verschuren, L. (author), van Duyvenvoorde, W. (author), Wong, K.E. (author), Keijer, J. (author), Bobeldijk-Pastorova, I. (author), Wielinga, P.Y. (author), Kleemann, R. (author)

Obesity characterized by adiposity and ectopic fat accumulation is associated with the development of non-alcoholic fatty liver disease (NAFLD). Treatments that stimulate lipid utilization may prevent the development of obesity and comorbidities. This study evaluated the potential anti-obesogenic hepatoprotective effects of combined treatment...

article 2019

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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

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Protective effect of rosiglitazone on kidney function in high-fat challenged human-CRP transgenic mice: A possible role for adiponectin and miR-21?

Morrison, M.C. (author), Yakala, G.K. (author), Liang, W. (author), Wielinga, P.Y. (author), Salic, K. (author), van Koppen, A. (author), Tomar, T. (author), Kleemann, R. (author), Heeringa, P. (author), Kooistra, T. (author)

Obesity-related albuminuria is associated with decline of kidney function and is considered a first sign of diabetic nephropathy. Suggested factors linking obesity to kidney dysfunction include low-grade inflammation, insulin resistance and adipokine dysregulation. Here, we investigated the effects of two pharmacological compounds with...

article 2017

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Butyrate restores HFD-induced adaptations in brain function and metabolism in mid-adult obese mice

Arnoldussen, I.A.C. (author), Wiesmann, M. (author), Pelgrim, C.E. (author), Wielemaker, E.M. (author), van Duyvenvoorde, W. (author), Amaral-Santos, P.L. (author), Verschuren, L. (author), Keijser, B.J.F. (author), Heerschap, A. (author), Kleemann, R. (author), Wielinga, P.Y. (author), Kiliaan, A.J. (author)

Objective: Midlife obesity affects cognition and increases risk of developing dementia. Recent data suggest that intake of the short chain fatty acid butyrate could improve memory function, and may protect against diet-induced obesity by reducing body weight and adiposity. Subjects: We examined the impact of a high-fat diet (HFD) followed by...

article 2017

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CAT-2003: A Novel Sterol Regulatory Element-Binding Protein Inhibitor That Reduces Steatohepatitis, Plasma Lipids, and Atherosclerosis in Apolipoprotein E*3-Leiden Mice

Zimmer, M. (author), Bista, P. (author), Benson, E.L. (author), Lee, D.Y. (author), Liu, F. (author), Picarella, D. (author), Vega, R.B. (author), Vu, C.B. (author), Yeager, M. (author), Ding, M. (author), Liang, G. (author), Horton, J.D. (author), Kleemann, R. (author), Kooistra, T. (author), Morrison, M.C. (author), Wielinga, P.Y. (author), Milne, J.C. (author), Jirousek, M.R. (author), Nichol, A.J. (author)

CAT-2003 is a novel conjugate of eicosapentaenoic acid (EPA) and niacin designed to be hydrolyzed by fatty acid amide hydrolase to release EPA inside cells at the endoplasmic reticulum. In cultured liver cells, CAT-2003 blocked the maturation of sterol regulatory element-binding protein (SREBP)-1 and SREBP-2 proteins and decreased the expression...

article 2017

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A casein hydrolysate based formulation attenuates obesity and associated non-alcoholic fatty liver disease and atherosclerosis in LDLr-/-.Leiden mice

Schoemaker, M.H. (author), Kleemann, R. (author), Morrison, M.C. (author), Verheij, J. (author), Salic, K. (author), van Tol, E.A.F. (author), Kooistra, T. (author), Wielinga, P.Y. (author)

Background: Obesity frequently associates with the development of non-alcoholic fatty liver disease (NAFLD) and atherosclerosis. Chronic inflammation in white adipose tissue (WAT) seems to be an important driver of these manifestations. Objective: This study investigated a combination of an extensively hydrolyzed casein (eHC), docosahexaenoic...

article 2017

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Surgical removal of inflamed epididymal white adipose tissue attenuates the development of non-alcoholic steatohepatitis in obesity

Mulder, P. (author), Morrison, M.C. (author), Wielinga, P.Y. (author), van Duyvenvoorde, W. (author), Kooistra, T. (author), Kleemann, R. (author)

Background: Non-alcoholic fatty liver disease (NAFLD) is strongly associated with abdominal obesity. Growing evidence suggests that inflammation in specific depots of white adipose tissue (WAT) has a key role in NAFLD progression, but experimental evidence for a causal role of WAT is lacking. Methods: A time-course study in C57BL/6J mice was...

article 2016

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Intervention with a caspase-1 inhibitor reduces obesity-associated hyperinsulinemia, non-alcoholic steatohepatitis (NASH) and hepatic fibrosis in LDLR-/-.Leiden mice

Morrison, M.C. (author), Mulder, P. (author), Salic, K. (author), Verheij, J. (author), Liang, W. (author), van Duyvenvoorde, W. (author), Menke, A. (author), Kooistra, T. (author), Kleemann, R. (author), Wielinga, P.Y. (author)

Background/objectives: Non-alcoholic steatohepatitis (NASH) is a serious liver condition, closely associated with obesity and insulin resistance. Recent studies have suggested an important role for inflammasome/caspase-1 in the development of NASH, but the potential therapeutic value of caspase-1 inhibition remains unclear. Therefore, we aimed...

article 2016

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Resolvin E1 attenuates atherosclerosis in absence of cholesterol-lowering effects and on top of atorvastatin

Salic, K. (author), Morrison, M.C. (author), Verschuren, L. (author), Wielinga, P.Y. (author), Wu, L. (author), Kleemann, R. (author), Gjorstrup, P. (author), Kooistra, T. (author)

Background and aims Besides LDL-cholesterol, local vascular inflammation plays a key role in atherogenesis. Efficient therapies to treat the inflammatory component of the disease have not been established. The discovery of specialized inflammation-resolving mediators, such as resolvins may provide new opportunities for treatment. This study...

article 2016

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Reduction of obesity-associated white adipose tissue inflammation by rosiglitazone is associated with reduced non-alcoholic fatty liver disease in LDLr-deficient mice

Mulder, P. (author), Morrison, M.C. (author), Verschuren, L. (author), Liang, W. (author), van Bockel, J.H. (author), Kooistra, T. (author), Wielinga, P.Y. (author), Kleemann, R. (author)

Obesity is associated with chronic low-grade inflammation that drives the development of metabolic diseases, including non-alcoholic fatty liver disease (NAFLD). We recently showed that white adipose tissue (WAT) constitutes an important source of inflammatory factors. Hence, interventions that attenuate WAT inflammation may reduce NAFLD...

article 2016

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Mirtoselect, an anthocyanin-rich bilberry extract, attenuates non-alcoholic steatohepatitis and associated fibrosis in ApoE∗3Leiden mice

Morrison, M.C. (author), Liang, W. (author), Mulder, P. (author), Verschuren, L. (author), Pieterman, E. (author), Toet, K. (author), Heeringa, P. (author), Wielinga, P.Y. (author), Kooistra, T. (author), Kleemann, R. (author)

Background & Aims Anthocyanins may have beneficial effects on lipid metabolism and inflammation and are demonstrated to have hepatoprotective properties in models of restraint-stress- and chemically-induced liver damage. However, their potential to protect against non-alcoholic steatohepatitis (NASH) under conditions relevant for human...

article 2015

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Replacement of Dietary Saturated Fat by PUFA-Rich Pumpkin Seed Oil Attenuates Non-Alcoholic Fatty Liver Disease and Atherosclerosis Development, with Additional Health Effects of Virgin over Refined Oil

Morrison, M.C. (author), Mulder, P. (author), Stavro, P.M. (author), Manuel Suárez, M. (author), Arola-Arnal, A. (author), van Duyvenvoorde, W. (author), Kooistra, T. (author), Wielinga, P.Y. (author), Kleemann, R. (author)

Background and Aims As dietary saturated fatty acids are associated with metabolic and cardiovascular disease, a potentially interesting strategy to reduce disease risk is modification of the quality of fat consumed. Vegetable oils represent an attractive target for intervention, as they largely determine the intake of dietary fats. Furthermore,...

article 2015

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A systems biology approach to understand the pathophysiological mechanisms of cardiac pathological hypertrophy associated with rosiglitazone

Verschuren, L. (author), Wielinga, P.Y. (author), Kelder, T. (author), Radonjic, M. (author), Salic, K. (author), Kleemann, R. (author), van Ommen, B. (author), Kooistra, T. (author)

Background : Cardiac pathological hypertrophy is associated with a significantly increased risk of coronary heart disease and has been observed in diabetic patients treated with rosiglitazone whereas most published studies do not suggest a similar increase in risk of cardiovascular events in pioglitazone-treated diabetic subjects. This study...

article 2014

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Effects of chocolate supplementation on metabolic and cardiovascular parameters in ApoE3L mice fed a high-cholesterol atherogenic diet

Yakala, G.K. (author), Wielinga, P.Y. (author), Suarez, M. (author), Bunschoten, A. (author), van Golde, J.M. (author), Arola, L. (author), Keijer, J. (author), Kleemann, R. (author), Kooistra, T. (author), Heeringa, P. (author)

Scope: Dietary intake of cocoa and/or chocolate has been suggested to exhibit protective cardiovascular effects although this is still controversial. The aim of this study was to investigate the effects of chocolate supplementation on metabolic and cardiovascular parameters. Methods and results: Four groups of ApoE*3Leiden mice were exposed to...

article 2013

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Coordinated and Interactive Expression of Genes of Lipid Metabolism and Inflammation in Adipose Tissue and Liver during Metabolic Overload

Liang, W. (author), Tonini, G. (author), Mulder, P. (author), Kelder, T. (author), van Erk, M. (author), van den Hoek, A.M. (author), Mariman, R. (author), Wielinga, P.Y. (author), Baccini, M. (author), Kooistra, T. (author), Biggeri, A. (author), Kleemann, R. (author)

Background:Chronic metabolic overload results in lipid accumulation and subsequent inflammation in white adipose tissue (WAT), often accompanied by non-alcoholic fatty liver disease (NAFLD). In response to metabolic overload, the expression of genes involved in lipid metabolism and inflammatory processes is adapted. However, it still remains...

article 2013

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Differential Effects of Drug Interventions and Dietary Lifestyle in Developing Type 2 Diabetes and Complications: A Systems Biology Analysis in LDLr-/- Mice

Radonjic, M. (author), Wielinga, P.Y. (author), Wopereis, S. (author), Kelder, T. (author), Goelela, V.S. (author), Verschuren, L. (author), Toet, K. (author), van Duyvenvoorde, W. (author), van der Werff van der Vat, B. (author), Stroeve, J.H.M. (author), Cnubben, N. (author), Kooistra, T. (author), van Ommen, B. (author), Kleemann, R. (author)

Excess caloric intake leads to metabolic overload and is associated with development of type 2 diabetes (T2DM). Current disease management concentrates on risk factors of the disease such as blood glucose, however with limited success. We hypothesize that normalizing blood glucose levels by itself is insufficient to reduce the development of...

article 2013

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Systems biology analysis unravels the complementary action of combined rosuvastatin and ezetimibe therapy

Verschuren, L. (author), Radonjic, M. (author), Wielinga, P.Y. (author), Kelder, T. (author), Kooistra, T. (author), van Ommen, B. (author), Kleemann, R. (author)

AIMS: Combination-drug therapy takes advantage of the complementary action of their individual components, thereby potentiating its therapeutic effect. Potential disadvantages include side effects that are not foreseen on basis of the data available from drug monotherapy. Here, we used a systems biology approach to understand both the efficacy...

article 2012

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Beneficial Effects of an Alternating High- Fat Dietary Regimen on Systemic Insulin Resistance, Hepatic and Renal Inflammation and Renal Function

Yakala, G.K. (author), van der Heijden, R. (author), Molema, G. (author), Schipper, M. (author), Wielinga, P.Y. (author), Kleemann, R. (author), Kooistra, T. (author), Heeringa, P. (author)

Background: An Alternating high- cholesterol dietary regimen has proven to be beneficial when compared to daily high- cholesterol feeding. In the current study we explored whether the same strategy is applicable to a high- fat dietary regimen. Objective: To investigate whether an alternating high- fat dietary regimen can effectively diminish...

article 2012

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Metabolic Stress–Induced Inflammation Plays a Major Role in the Development of Osteoarthritis in Mice

Gierman, L.M. (author), van der Ham, F. (author), Koudijs, A. (author), Wielinga, P.Y. (author), Kleemann, R. (author), Kooistra, T. (author), Stoop, R. (author), Kloppenburg, M. (author), van Osch, G.J.V.M. (author), Stojanovic-Susulic, V. (author), Huizinga, T.W. (author), Zuurmond, A.M. (author)

article 2012