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(Pro)Renin Receptor Antagonism Attenuates High-Fat-Diet–Induced Hepatic Steatosis

Gayban, A.J.B. (author), Souza, L.A.C. (author), Cooper, S.G. (author), Regalado, E. (author), Kleemann, R. (author), Earley, Y.F. (author)

Non-alcoholic fatty liver disease (NAFLD) comprises a spectrum of liver damage directly related to diabetes, obesity, and metabolic syndrome. The (pro)renin receptor (PRR) has recently been demonstrated to play a role in glucose and lipid metabolism. Here, we test the hypothesis that the PRR regulates the development of diet-induced hepatic...

article 2023

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Correction to: Toxicogenomics directory of chemically exposed human hepatocytes

Grinberg, M. (author), Stöber, R.M. (author), Edlund, K. (author), Rempel, E. (author), Godoy, P. (author), Reif, R. (author), Widera, A. (author), Madjar, K. (author), Schmidt-Heck, W. (author), Marchan, R. (author), Sachinidis, A. (author), Spitkovsky, D. (author), Hescheler, J. (author), Carmo, H. (author), Arbo, M.D. (author), van de Water, B. (author), Wink, S. (author), Vinken, M. (author), Rogiers, V. (author), Escher, S. (author), Hardy, B. (author), Mitic, D. (author), Myatt, G. (author), Waldmann, T. (author), Mardinoglu, A. (author), Damm, G. (author), Seehofer, D. (author), Nüssler, A. (author), Weiss, T.S. (author), Oberemm, A. (author), Lampen, A. (author), Schaap, M.M. (author), Luijten, M. (author), van Steeg, H. (author), Thasler, W.E. (author), Kleinjans, J.C.S. (author), Stierum, R.H. (author), Leist, M. (author), Rahnenführer, J. (author), Hengstler, J.G. (author)

Correction to: Arch Toxicol (2014) 88:2261–2287 https://doi.org/10.1007/s00204-014-1400-x.

article 2022

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Synergistic Effect of Feeding Time and Diet on Hepatic Steatosis and Gene Expression in Male Wistar Rats

Oosterman, J.E. (author), Koekkoek, L.L. (author), Foppen, E. (author), Unmehopa, U.A. (author), Eggels, L. (author), Verheij, J. (author), Fliers, E. (author), la Fleur, S.E. (author), Kalsbeek, A. (author)

Objective. Eating out of phase with the endogenous biological clock alters clock and metabolic gene expression in rodents and can induce obesity and type 2 diabetes mellitus. Diet composition can also affect clock gene expression. Here, we assessed the combined effect of diet composition and feeding time on (1) body composition, (2) energy...

article 2020

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A 12-wk whole-grain wheat intervention protects against hepatic fat: The Graandioos study, a randomized trial in overweight subjects

Schutte, S. (author), Esser, D. (author), Hoevenaars, F.P.M. (author), Hooiveld, G.J.E.J. (author), Priebe, M.G. (author), Vonk, R.J. (author), Wopereis, S. (author), Afman, L.A. (author)

Background: Whole-grain wheat (WGW) is described as nutritionally superior to refined wheat (RW) and thus advocated as the healthy choice, although evidence from intervention studies is often inconsistent. The liver, as the central organ in energy metabolism, might be an important target organ for WGW interventions. Objective: The aim of this...

article 2018

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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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Are zebrafish larvae suitable for assessing the hepatotoxicity potential of drug candidates?

Mesens, N. (author), Crawfordb, A.D. (author), Menke, A. (author), Hung, P.D. (author), van Goethem, F. (author), Nuyts, R. (author), Hansen, E. (author), Wolterbeek, A. (author), van Gompel, J. (author), de Witte, P. (author), Esguerra, C.V. (author)

Drug-induced liver injury (DILI) is poorly predicted by single-cell-based assays, probably because of the lack of physiological interactions with other cells within the liver. An intact whole liver system such as one present in zebrafish larvae could provide added value in a screening strategy for DILI; however, the possible occurrence of other...

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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Toxicogenomics directory of chemically exposed human hepatocytes

Grinberg, M. (author), Stöber, R.M. (author), Edlund, K. (author), Rempel, E. (author), Godoy, P. (author), Reif, R. (author), Widera, A. (author), Madjar, K. (author), Schmidt-Heck, W. (author), Marchan, R. (author), Sachinidis, A. (author), Spitkovsky, D. (author), Hescheler, J. (author), Carmo, H. (author), Arbo, M.D. (author), van de Water, B. (author), Wink, S. (author), Vinken, M. (author), Rogiers, V. (author), Escher, S. (author), Hardy, B. (author), Mitic, D. (author), Myatt, G. (author), Waldmann, T. (author), Mardinoglu, A. (author), Damm, G. (author), Seehofer, D. (author), Nüssler, A. (author), Weiss, T.S. (author), Oberemm, A. (author), Lampen, A. (author), Schaap, M.M. (author), Luijten, M. (author), van Steeg, H. (author), Thasler, W.E. (author), Kleinjans, J.C.S. (author), Stierum, R.H. (author), Leist, M. (author), Rahnenführer, J. (author), Hengstler, J.G. (author)

A long-term goal of numerous research projects is to identify biomarkers for in vitro systems predicting toxicity in vivo. Often, transcriptomics data are used to identify candidates for further evaluation. However, a systematic directory summarizing key features of chemically influenced genes in human hepatocytes is not yet available. To bridge...

article 2014

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Metabolically induced liver inflammation leads to NASH and differs from LPS-or IL-1β-induced chronic inflammation

Liang, W. (author), Lindeman, J.H. (author), Menke, A.L. (author), Koonen, D.P. (author), Morrison, M. (author), Havekes, L.M. (author), van den Hoek, A.M. (author), Kleemann, R. (author)

The nature of the chronic inflammatory component that drives the development of non-alcoholic steatohepatitis (NASH) is unclear and possible inflammatory triggers have not been investigated systematically. We examined the effect of non-metabolic triggers (lipopolysaccharide (LPS), interleukin-1β (IL-1β), administered by slow-release minipumps)...

article 2014

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Establishment of a general NAFLD scoring system for rodent models and comparison to human liver pathology

Liang, W. (author), Menke, A.L. (author), Driessen, A. (author), Koek, G.H. (author), Lindeman, J.H. (author), Stoop, R. (author), Havekes, L.M. (author), Kleemann., R. (author), van den Hoek, A.M. (author)

Results: The criteria macrovesicular steatosis, microvesicular steatosis, hepatocellular hypertrophy, inflammation and fibrosis were generally applicable to rodent NAFLD. The inter-observer reproducibility (evaluated using the Intraclass Correlation Coefficient) between the ten observers was high for the analysis of macrovesicular steatosis and...

article 2014

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The comparison of lipid profiling in mouse brain and liver after starvation and a high-fat diet: A medical systems biology approach

van Ginneken, V.J.T. (author), Verheij, E. (author), Hekman, M. (author), van der Greef, J. (author), Feskens, E.J.M. (author), Poelmann, R.E. (author)

We investigated with LC-MS techniques, measuring approximately 109 lipid compounds, in mouse brain and liver tissue after 48 hours of starvation and a High-Fat Diet if brain and liver lipid composition changed. We measured Cholesterolesters (ChE), Lysophosphatidyl-cholines (LPC), Phosphatidylcholine (PC), Sphingomyelin (SPM) and Triacylglycerols...

bookPart 2011

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Metabolomics (liver and blood profiling) in a mouse model in response to fasting: A study of hepatic steatosis

van Ginneken, V. (author), Verhey, E. (author), Poelmann, R. (author), Ramakers, R. (author), van Dijk, K.W. (author), Ham, L. (author), Voshol, P. (author), Havekes, L. (author), van Eck, M. (author), van der Greef, J. (author), TNO Kwaliteit van Leven (author)

A metabolomic approach was applied to a mouse model of starvation-induced hepatic steatosis. After 24 h of fasting it appears that starvation reduced the phospholipids (PL), free cholesterol (FC), and cholesterol esters (CE) content of low-density lipoproteins (LDL). In liver lipid profiles major changes were observed using different techniques....

article 2007

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Uniform procedure of 1H NMR analysis of rat urine and toxicometabonomics Part II: Comparison of NMR profiles classification of hepatotoxicity

Schoonen, W.G.E.J. (author), Kloks, C.P.A.M. (author), Ploemen, J.-P.H.T.M. (author), Smit, M.J. (author), Zandberg, P. (author), Horbach, G.J. (author), Mellema, J.-R. (author), van Zuylen, C.T. (author), Tas, A.C. (author), van Nesselrooij, J.H.J. (author), Vogels, J.T.W.E. (author), TNO Kwaliteit van Leven (author)

A procedure of nuclear magnetic resonance (NMR) urinalysis using pattern recognition is proposed for early detection of toxicity of investigational compounds in rats. The method is applied to detect toxicity upon administration of 13 toxic reference compounds and one nontoxic control compound (mianserine) in rats. The toxic compounds are...

article 2007

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Dietary sphingolipids lower plasma cholesterol and triacylglycerol and prevent liver steatosis

Nieuwenhuizen, W.F. (author), Duivenvoorden, I. (author), Voshol, P.J. (author), Rensen, P.C.N. (author), van Duyvenvoorde, W. (author), Romijn, J.A. (author), Emeis, J.J. (author), Havekes, L.M. (author), TNO Kwaliteit van Leven (author)

The prevalence of dyslipidemia and obesity resulting from excess energy intake and physical inactivity is increasing. The liver plays a pivotal role in the systemic lipid homeostasis. Effective, natural dietary interventions that lower plasma lipids and promote liver health are needed. APOE*3Leiden mice were fed a Western-type diet, supplemented...

article 2007

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Sustained activation of the mammalian target of rapamycin nutrient sensing pathway is associated with hepatic insulin resistance, but not with steatosis, in mice

Korsheninnikova, E. (author), van der Zon, G.C.M. (author), Voshol, P.J. (author), Janssen, G.M. (author), Havekes, L.M. (author), Grefhorst, A. (author), Kuipers, F. (author), Reijngoud, D.-J. (author), Romijn, J.A. (author), Ouwens, D.M. (author), Maassen, J.A. (author), TNO Kwaliteit van Leven (author)

Aims/hypothesis: Activation of nutrient sensing through mammalian target of rapamycin (mTOR) has been linked to the pathogenesis of insulin resistance. We examined activation of mTOR-signalling in relation to insulin resistance and hepatic steatosis in mice. Materials and methods: Chronic hepatic steatosis and hepatic insulin resistance were...

article 2006

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Endogenous interleukin-10 protects against hepatic steatosis but does not improve insulin sensitivity during high-fat feeding in mice

den Boer, M.A.M. (author), Voshol, P.J. (author), Schröder-van Der Elst, J.P. (author), Korsheninnikova, E. (author), Ouwens, D.M. (author), Kuipers, F. (author), Havekes, L.M. (author), Romijn, J.A. (author), TNO Kwaliteit van Leven (author)

Several studies have demonstrated an association in humans between plasma levels or production capacity of the antiinflammatory cytokine IL-10 and insulin sensitivity. The aim of our study was to investigate the protective role of endogenous IL-10 availability in the development of diet-induced insulin resistance. We compared parameters of...

article 2006

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Dietary sphingolipids lower plasma cholesterol and triacylglycerol and prevent liver steatosis in APOE*3Leiden mice

Duivenvoorden, I. (author), Voshol, P.J. (author), Rensen, P.C.N. (author), van Duyvenvoorde, W. (author), Romijn, J.A. (author), Emeis, J.J. (author), Havekes, L.M. (author), Nieuwenhuizen, W.F. (author), TNO Kwaliteit van Leven (author)

Background: The prevalence of dyslipidemia and obesity resulting from excess energy intake and physical inactivity is increasing. The liver plays a pivotal role in systemic lipid homeostasis. Effective, natural dietary interventions that lower plasma lipids and promote liver health are needed. Objective: Our goal was to determine the effect of...

article 2006

document

Differential effects of pharmacological liver X receptor activation on hepatic and peripheral insulin sensitivity in lean and ob/ob mice

TNO Kwaliteit van Leven (author), Grefhorst, A. (author), van Dijk, T.H. (author), Hammer, A. (author), van der Sluijs, F.H. (author), Havinga, R. (author), Havekes, L.M. (author), Romijn, J.A. (author), Groot, P.H. (author), Reijngoud, D.J. (author), Kuipers, F. (author)

Liver X receptor (LXR) agonists have been proposed to act as anti-diabetic drugs. However, pharmacological LXR activation leads to severe hepatic steatosis, a condition usually associated with insulin resistance and type 2 diabetes mellitus. To address this apparent contradiction, lean and ob/ob mice were treated with the LXR agonist GW-3965 for...

article 2005

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Sixteen hours of fasting differentially affects hepatic and muscle insulin sensitivity in mice

TNO Kwaliteit van Leven (author), Heijboer, A.C. (author), Donga, E. (author), Voshol, P.J. (author), Dang, Z.C. (author), Havekes, L.M. (author), Romijn, J.A. (author), Corssmit, E.P.M. (author)

Fasting readily induces hepatic steatosis. Hepatic steatosis is associated with hepatic insulin resistance. The purpose of the present study was to document the effects of 16 h of fasting in wild-type mice on insulin sensitivity in liver and skeletal muscle in relation to 1) tissue accumulation of triglycerides (TGs) and 2) changes in mRNA...

article 2005

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Acute inhibition of hepatic beta-oxidation in APOE*3Leiden mice does not affect hepatic VLDL secretion or insulin sensitivity

TNO Kwaliteit van Leven (author), Duivenvoorden, I. (author), Teusink, B. (author), Rensen, P.C.N. (author), Kuipers, F. (author), Romijn, J.A. (author), Havekes, L.M. (author), Voshol, P.J. (author)

Hepatic VLDL and glucose production is enhanced in type 2 diabetes and associated with hepatic steatosis. Whether the derangements in hepatic metabolism are attributable to steatosis or to the increased availability of FA metabolites is not known. We used methyl palmoxirate (MP), an inhibitor of carnitine palmitoyl transferase I, to acutely...

article 2005