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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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Prolonged high-fat diet induces gradual and fat depot-specific DNA methylation changes in adult mice

Slieker, R.C. (author), Mulder, P.C.A. (author), Zoetemelk, I. (author), Verschuren, L. (author), Suchiman, H.E.D. (author), Toet, K.H. (author), Droog, S. (author), Slagboom, P.E. (author), Kooistra, T. (author), Kleemann, R. (author), Heijmans, B.T. (author)

High-fat diets (HFD) are thought to contribute to the development of metabolism-related diseases. The long-term impact of HFD may be mediated by epigenetic mechanisms, and indeed, HFD has been reported to induce DNA methylation changes in white adipose tissue (WAT) near metabolism related genes. However, previous studies were limited to a single...

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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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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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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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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Defective postreperfusion metabolic recovery directly associates with incident delayed graft function

Wijermars, L.G.M. (author), Schaapherder, A.F. (author), de Vries, D.K. (author), Verschuren, L. (author), Wüst, R.C.I. (author), Kostidis, S. (author), Mayboroda, O.A. (author), Prins, F. (author), Ringers, J. (author), Bierau, J. (author), Bakker, J.A. (author), Kooistra, T. (author), Lindeman, J.H.N. (author)

Delayed graft function (DGF) following kidney transplantation affects long-term graft function and survival and is considered a manifestation of ischemia reperfusion injury. Preclinical studies characterize metabolic defects resulting from mitochondrial damage as primary driver of ischemia reperfusion injury. In a comprehensive approach that...

article 2016

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Early intake of long-chain polyunsaturated fatty acids preserves brain structure and function in diet-induced obesity

Arnoldussen, I.A.C. (author), Zerbi, V. (author), Wiesmann, M. (author), Noordman, R.H.J. (author), Bolijn, S. (author), Mutsaers, M.P.C. (author), Dederen, P.J.W.C. (author), Kleemann, R. (author), Kooistra, T. (author), van Tol, E.A.F. (author), Gross, G. (author), Schoemaker, M.H. (author), Wieling, P.Y. (author), Kilian, A. (author)

orldwide, the incidence of obesity is increasing at an alarming rate, and the number of children with obesity is especially worrisome. These developments raise concerns about the physical, psychosocial and cognitive consequences of obesity. It was shown that early dietary intake of arachidonic acid (ARA) and docosahexaenoic acid (DHA) can reduce...

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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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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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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Quantifying phenotypic flexibility as the response to a high-fat challenge test in different states of metabolic health

Kardinaal, A.F.M. (author), van Erk, M.J. (author), Dutman, A.E. (author), Stroeve, J.H.M. (author), van de Steeg, E. (author), Bijlsma, S. (author), Kooistra, T. (author), van Ommen, B. (author), Wopereis, S. (author)

Metabolism maintains homeostasis at chronic hypercaloric conditions, activating postprandial response mechanisms, which come at the cost of adaptation processes such as energy storage, eventually with negative health consequences. This study quantified the metabolic adaptation capacity by studying challenge response curves. After a high-fat...

article 2015

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Beneficial Effects of a Nutritional Composition on Diabetic Risk Factors and Complications in LDLr-/-. Leiden Mice

Schoemaker, M. (author), van Tol, E. (author), Kooistra, T. (author), Kleemann, R. (author), Wielinga, P. (author)

Obesity frequently associates with chronic inflammatory diseases, including type 2 diabetes. In this study, a combination of a protein hydrolysate, LCPUFAs and a probiotic strain was investigated on the development of high fat diet -induced diabetic risk factors and complications in LDLr-/-.Leiden mice. Male LDLr-/-.Leiden mice at 12 wks of age...

article 2015

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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

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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Epicatechin attenuates atherosclerosis and exerts anti-inflammatory effects on diet-induced human-CRP and NFκB invivo

Morrison, M. (author), van der Heijden, R. (author), Heeringa, P. (author), Kaijzel, E. (author), Verschuren, L. (author), Blomhoff, R. (author), Kooistra, T. (author), Kleemann, R. (author)

Objective: Previous studies investigating flavanol-rich foods provide indications for potential cardioprotective effects of these foods, but the effects of individual flavanols remain unclear. We investigated whether the flavanol epicatechin can reduce diet-induced atherosclerosis, with particular emphasis on the cardiovascular risk factors...

article 2014

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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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Effects of probiotic Lactobacillus rhamnosus GG and Propionibacterium freudenreichii ssp. shermanii JS supplementation on intestinal and systemic markers of inflammation in ApoE*3Leiden mice consuming a high-fat diet

Oksaharju, A. (author), Kooistra, T. (author), Kleemann, R. (author), van Duyvenvoorde, W. (author), Miettinen, M. (author), Lappalainen, J. (author), Lindstedt, K.A. (author), Kovanen, P.T. (author), Korpela, R. (author), Kekkonen, R.A. (author)

A high-fat diet disturbs the composition and function of the gut microbiota and generates local gut-associated and also systemic responses. Intestinal mast cells, for their part, secrete mediators which play a role in the orchestration of physiological and immunological functions of the intestine. Probiotic bacteria, again, help to maintain the...

article 2013