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van Dam, A.D. (author), Nahon, K.J. (author), Kooijman, S. (author), van den Berg, S.M. (author), Kanhai, A.A. (author), Kikuchi, T. (author), Heemskerk, M.M. (author), van Harmelen, V. (author), Lombès, M. (author), van den Hoek, A.M. (author), de Winther, M.P. (author), Lutgens, E. (author), Guigas, B. (author), Rensen, P.C. (author), Boon, M.R. (author)Salsalate improves glucose intolerance and dyslipidemia in type 2 diabetes patients, but the mechanism is still unknown. The aim of the current study was to unravel the molecular mechanisms involved in these beneficial metabolic effects of salsalate by treating mice with salsalate during and after development of high-fat diet-induced obesity. We...article 2015
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Berbeé, J.F.P. (author), Boon, M.R. (author), Khedoe, P.P.S.J. (author), Bartelt, A. (author), Schlein, C. (author), Worthmann, A. (author), Kooijman, S. (author), Hoeke, G. (author), Mol, I.M. (author), John, C. (author), Jung, C. (author), Vazirpanah, N. (author), Brouwers, L.P.J. (author), Gordts, P.L.S.M. (author), Esko, J.D. (author), Hiemstra, P.S. (author), Havekes, L.M. (author), Scheja, L. (author), Heeren, J. (author), Rensen, P.C.N. (author)Brown adipose tissue (BAT) combusts high amounts of fatty acids, thereby lowering plasma triglyceride levels and reducing obesity. However, the precise role of BAT in plasma cholesterol metabolism and atherosclerosis development remains unclear. Here we show that BAT activation by b3-adrenergic receptor stimulation protects from atherosclerosis...article 2015
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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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Derous, D. (author), Kelder, T. (author), van Schothorst, E.M. (author), van Erk, M. (author), Voigt, A. (author), Klaus, S. (author), Keijer, J. (author), Radonjic, M. (author)Health is influenced by interplay of molecular, physiological and environmental factors. To effectively maintain health and prevent disease, health-relevant relations need to be understood at multiple levels of biological complexity. Network-based methods provide a powerful platform for integration and mining of data and knowledge characterizing...article 2015
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Wagner, A. (author), Cohen, N. (author), Kelder, T. (author), Amit, U. (author), Liebman, E. (author), Steinberg, D.M. (author), Radonjic, M. (author), Ruppin, E. (author)High-throughput omics have proven invaluable in studying human disease, and yet day-to-day clinical practice still relies on physiological, non-omic markers. The metabolic syndrome, for example, is diagnosed and monitored by blood and urine indices such as blood cholesterol levels. Nevertheless, the association between the molecular and the...article 2015
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Heemskerk, M.M. (author), van den Berg, S.A. (author), Pronk, A.C.M. (author), van Klinken, J.B. (author), Boon, M.R. (author), Havekes, L.M. (author), Rensen, P.C.N. (author), Willems van Dijk, K. (author), van Harmelen, V. (author)The lipid-lowering effect of niacin has been attributed to the inhibition of cAMP production in adipocytes, thereby inhibiting intracellular lipolysis and release of nonesterified fatty acids (NEFA) to the circulation. However, long-term niacin treatment leads to a normalization of plasma NEFA levels and induces insulin resistance, for which the...article 2014
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Schols, R.M. (author), ter Laan, M. (author), Stassen, L.P.S. (author), Bouvy, N.D. (author), Amelink, A. (author), Wieringa, F.P. (author), Alic, L. (author)Background: Intraoperative nerve localization is of great importance in surgery. In certain procedures, where nerves show visual resemblance to surrounding adipose tissue, this can be particularly challenging for the human eye. An example of such a delicate procedure is thyroid and parathyroid surgery, where iatrogenic injury of the recurrent...article 2014
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Bakker, L.E.H. (author), Boon, M.R. (author), van der Linden, R.A.D. (author), Arias-Bouda, L.P. (author), van Klinken, J.B. (author), Smit, F. (author), Verberne, H.J. (author), Jukema, J.W. (author), Tamsma, J.T. (author), Havekes, L.M. (author), van Marken Lichtenbelt, W.D. (author), Jazet, I.M. (author), Rensen, P.C.N. (author)Background: Individuals of south Asian origin have a very high risk of developing type 2 diabetes compared with white Caucasians. We aimed to assess volume and activity of brown adipose tissue (BAT), which is thought to have a role in energy metabolism by combusting fatty acids and glucose to produce heat and might contribute to the difference...article 2014
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Geerling, J.J. (author), Boon, M.R. (author), Kooijman, S. (author), Parlevliet, E.T. (author), Havekes, L.M. (author), Romijn, J.A. (author), Meurs, I.M. (author), Rensen, P.C.N. (author)Abstract Important players in triglyceride (TG) metabolism include the liver (production), white adipose tissue (WAT) (storage), heart and skeletal muscle (combustion to generate ATP), and brown adipose tissue (BAT) (combustion toward heat), the collective action of which determine plasma TG levels. Interestingly, recent evidence points to a...article 2014
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Kooijman, S. (author), Boon, M.R. (author), Parlevliet, E.T. (author), Geerling, J.J. (author), van de Pol, V. (author), Romijn, J.A. (author), Havekes, L.M. (author), Meurs, I. (author), Rensen, P.C.N. (author)The melanocortin system is an important regulator of energy balance, and melanocortin 4 receptor (MC4R) deficiency is the most common monogenic cause of obesity. We investigated whether the relationship between melanocortin system activity and energy expenditure (EE) is mediated by brown adipose tissue (BAT) activity. Therefore, female APOE∗3...article 2014
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Sugimoto-Kawabata, K. (author), Shimada, H. (author), Sakai, K. (author), Suzuki, K. (author), Kelder, T. (author), Pieterman, E.J. (author), Cohen, L.H. (author), Havekes, L.M. (author), Princen, H.M. (author), van den Hoek, A.M. (author)Bile acid sequestrants (BASs) are cholesterollowering drugs that also affect hyperglycemia. The mechanism by which BASs exert these and other metabolic effects beyond cholesterol lowering remains poorly understood. The present study aimed to investigate the effects of a BAS, colestilan, on body weight, energy expenditure, and glucose and lipid...article 2013
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Al-Lahham, S. (author), Roelofsen, H. (author), Rezaee, F. (author), Weening, D. (author), Hoek, A. (author), Vonk, R. (author), Venema, K. (author)Background Adipose tissue is a primary site of obesity-induced inflammation, which is emerging as an important contributor to obesity-related diseases such as type 2 diabetes. Dietary fibre consumption appears to be protective. Short-chain fatty acids, e.g. propionic acid, are the principal products of the colonic fermentation of dietary fibre...article 2012
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Wielinga, P.Y., (author), Harthoorn, L.F., (author), Verschuren, L., (author), Schoemaker, M.H., (author), Jouni, Z.E., (author), van, Tol, E.A.F. (author), Kleemann, R., (author), Kooistra, T. (author)Scope: This study addresses whether early life arachidonic acid (ARA)/docosahexaenoic acid (DHA) supplementation or eicosapentaenoic acid (EPA)/DHA (Omacor) supplementation affects body weight gain, lipid metabolism, and adipose tissue quantity and quality in later life in ApoE*3Leiden-transgenic mice, a humanized model for hyperlipidemia and...article 2012
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Gaubius Instituut TNO (author), Coomans, C.P. (author), Geerling, J.J. (author), Guigas, B. (author), van den Hoek, A.M. (author), Parlevliet, E.T. (author), Ouwens, D.M. (author), Pijl, H. (author), Voshol, P.J. (author), Rensen, P.C.N. (author), Havekes, L.M. (author), Romijn, J.A. (author)Insulin signaling in the central nervous system (CNS) is required for the inhibitory effect of insulin on glucose production. Our aim was to determine whether the CNS is also involved in the stimulatory effect of circulating insulin on the tissue-specific retention of fatty acid (FA) from plasma. In wild-type mice, hyperinsulinemic-euglycemic...article 2011
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Coomans, C.P. (author), Biermasz, N.R. (author), Geerling, J.J. (author), Guigas, B. (author), Rensen, P.C.N. (author), Havekes, L.M. (author), Romijn, J.A. (author)OBJECTIVE - Insulin inhibits endogenous glucose production (EGP) and stimulates glucose uptake in peripheral tissues. Hypothalamic insulin signaling is required for the inhibitory effects of insulin on EGP. We examined the contribution of central insulin signaling on circulating insulin-stimulated tissue-specific glucose uptake. RESEARCH DESIGN...article 2011
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Al-Lahham, S.H. (author), Roelofsen, H. (author), Priebe, M. (author), Weening, D. (author), Dijkstra, M. (author), Hoek, A. (author), Rezaee, F. (author), Venema, K. (author), Vonk, R.J. (author), TNO Kwaliteit van Leven (author)Background Dietary fibre (DF) has been shown to be protective for the development of obesity, insulin resistance and type 2 diabetes. Short-chain fatty acids, produced by colonic fermentation of DF might mediate this beneficial effect. Adipose tissue plays a key role in the regulation of energy homeostasis, therefore, we investigated the...article 2010
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Bakker, G.C.M. (author), van Erk, M.J. (author), Pellis, L. (author), Wopereis, S. (author), Rubingh, C.M. (author), Cnubben, N.H.P. (author), Kooistra, T. (author), van Ommen, B. (author), Hendriks, H.F.J. (author), TNO Kwaliteit van Leven (author)Background: Low-grade chronic inflammation in overweight subjects is thought to play an important role in disease development. Objective: It was hypothesized that specific dietary components are able to reduce low-grade inflammation as well as metabolic and oxidative stress. Design: Dietary products [resveratrol, green tea extract, α-tocopherol,...article 2010
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TNO Kwaliteit van Leven (author), Kleemann, R. (author), van Erk, M. (author), Verschuren, L. (author), van den Hoek, A.M. (author), Koek, M. (author), Wielinga, P.Y. (author), Jie, A. (author), Pellis, L. (author), Bobeldijk-Pastorova, I. (author), Kelder, T. (author), Toet, K. (author), Wopereis, S. (author), Cnubben, N. (author), Evelo, C. (author), van Ommen, B. (author), Kooistra, T. (author)BACKGROUND: The sequence of events leading to the development of insulin resistance (IR) as well as the underlying pathophysiological mechanisms are incompletely understood. As reductionist approaches have been largely unsuccessful in providing an understanding of the pathogenesis of IR, there is a need for an integrative, time-resolved approach...article 2010
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TNO Kwaliteit van Leven (author), Bijland, S. (author), Pieterman, E.J. (author), Maas, A.C.E. (author), van der Hoorn, J.W.A. (author), van Erk, M.J. (author), van Klinken, J.B. (author), Havekes, L.M. (author), van Dijk, K.W. (author), Princen, H.M.G. (author), Rensen, P.C.N. (author)The peroxisome proliferator-activated receptor alpha (PPARalpha) activator fenofibrate efficiently decreases plasma triglycerides (TG), which is generally attributed to enhanced very low density lipoprotein (VLDL)-TG clearance and decreased VLDL-TG production. However, because data on the effect of fenofibrate on VLDL production are...article 2010
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Knippenberg, M. (author), Helder, M.N. (author), Doulabi, B.Z. (author), Bank, R.A. (author), Wuisman, P.I.J.M. (author), Klein-Nulend, J. (author), TNO Kwaliteit van Leven (author)Adipose tissue-derived mesenchymal stem cells (AT-MSCs) in combination with bone morphogenetic protein-2 (BMP-2) or transforming growth factor-β1 (TGF-β1) are under evaluation for bone tissue engineering. Posttranslational modification of type I collagen is essential for functional bone tissue with adequate physical and mechanical properties. We...article 2009