Aldo Grefhorst

Summary

Affiliation: University Medical Center Groningen
Country: The Netherlands

Publications

  1. ncbi Acute hepatic steatosis in mice by blocking beta-oxidation does not reduce insulin sensitivity of very-low-density lipoprotein production
    Aldo Grefhorst
    Center for Liver, Digestive and Metabolic Diseases, Laboratory of Pediatrics, Univ Medical Center Groningen, Groningen, The Netherlands
    Am J Physiol Gastrointest Liver Physiol 289:G592-8. 2005
  2. pmc Reduced insulin-mediated inhibition of VLDL secretion upon pharmacological activation of the liver X receptor in mice
    Aldo Grefhorst
    Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
    J Lipid Res 50:1374-83. 2009
  3. ncbi Differential effects of pharmacological liver X receptor activation on hepatic and peripheral insulin sensitivity in lean and ob/ob mice
    Aldo Grefhorst
    Center for Liver, Digestive, and Metabolic Diseases, Laboratory of Pediatrics, Rm Y2117, CMC IV, Univ Medical Center Groningen, P O Box 30 001, 9700 RB Groningen, The Netherlands
    Am J Physiol Endocrinol Metab 289:E829-38. 2005
  4. doi Carbohydrate-response-element-binding protein (ChREBP) and not the liver X receptor α (LXRα) mediates elevated hepatic lipogenic gene expression in a mouse model of glycogen storage disease type 1
    Aldo Grefhorst
    Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
    Biochem J 432:249-54. 2010
  5. doi Lxralpha deficiency hampers the hepatic adaptive response to fasting in mice
    Maaike H Oosterveer
    Departments of Pediatrics and Laboratory Medicine, Center for Liver Digestive and Metabolic Diseases, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
    J Biol Chem 283:25437-45. 2008
  6. doi Chronic prednisolone treatment reduces hepatic insulin sensitivity while perturbing the fed-to-fasting transition in mice
    Anke J Laskewitz
    Department of Pediatrics, Center for Liver Digestive and Metabolic Diseases, University Medical Center Groningen, RB Groningen, The Netherlands
    Endocrinology 151:2171-8. 2010
  7. pmc Fenofibrate simultaneously induces hepatic fatty acid oxidation, synthesis, and elongation in mice
    Maaike H Oosterveer
    Department of Pediatrics, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands
    J Biol Chem 284:34036-44. 2009
  8. pmc An increased flux through the glucose 6-phosphate pool in enterocytes delays glucose absorption in Fxr-/- mice
    Theo H van Dijk
    Departments of Laboratory Medicine and Pediatrics, Center for Liver Digestive and Metabolic Diseases, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands
    J Biol Chem 284:10315-23. 2009
  9. doi Inhibition of mitochondrial fatty acid oxidation in vivo only slightly suppresses gluconeogenesis but enhances clearance of glucose in mice
    Terry G J Derks
    Department of Pediatrics, Laboratory of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
    Hepatology 47:1032-42. 2008
  10. doi Chronic prednisolone treatment aggravates hyperglycemia in mice fed a high-fat diet but does not worsen dietary fat-induced insulin resistance
    Anke J Laskewitz
    Department of Pediatrics, University of Groningen, University Medical Center Groningen, 9700 RB, Groningen, The Netherlands
    Endocrinology 153:3713-23. 2012

Collaborators

Detail Information

Publications23

  1. ncbi Acute hepatic steatosis in mice by blocking beta-oxidation does not reduce insulin sensitivity of very-low-density lipoprotein production
    Aldo Grefhorst
    Center for Liver, Digestive and Metabolic Diseases, Laboratory of Pediatrics, Univ Medical Center Groningen, Groningen, The Netherlands
    Am J Physiol Gastrointest Liver Physiol 289:G592-8. 2005
    ....
  2. pmc Reduced insulin-mediated inhibition of VLDL secretion upon pharmacological activation of the liver X receptor in mice
    Aldo Grefhorst
    Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
    J Lipid Res 50:1374-83. 2009
    ..In conclusion, the effects of LXR activation by T0901317 on lipid metabolism can override the normal control of insulin to suppress VLDL particle secretion...
  3. ncbi Differential effects of pharmacological liver X receptor activation on hepatic and peripheral insulin sensitivity in lean and ob/ob mice
    Aldo Grefhorst
    Center for Liver, Digestive, and Metabolic Diseases, Laboratory of Pediatrics, Rm Y2117, CMC IV, Univ Medical Center Groningen, P O Box 30 001, 9700 RB Groningen, The Netherlands
    Am J Physiol Endocrinol Metab 289:E829-38. 2005
    ..Remarkably, steatosis associated with LXR activation did not affect hepatic insulin sensitivity...
  4. doi Carbohydrate-response-element-binding protein (ChREBP) and not the liver X receptor α (LXRα) mediates elevated hepatic lipogenic gene expression in a mouse model of glycogen storage disease type 1
    Aldo Grefhorst
    Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
    Biochem J 432:249-54. 2010
    ..Thus ChREBP is an attractive target to alleviate derangements in lipid metabolism observed in patients with GSD-1...
  5. doi Lxralpha deficiency hampers the hepatic adaptive response to fasting in mice
    Maaike H Oosterveer
    Departments of Pediatrics and Laboratory Medicine, Center for Liver Digestive and Metabolic Diseases, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
    J Biol Chem 283:25437-45. 2008
    ..In summary, these studies identify LXRalpha as a physiologically relevant mediator of the hepatic response to fasting. However, the data do not support a role for LXR in hepatic glucose sensing...
  6. doi Chronic prednisolone treatment reduces hepatic insulin sensitivity while perturbing the fed-to-fasting transition in mice
    Anke J Laskewitz
    Department of Pediatrics, Center for Liver Digestive and Metabolic Diseases, University Medical Center Groningen, RB Groningen, The Netherlands
    Endocrinology 151:2171-8. 2010
    ..In conclusion, these results indicate that chronic prednisolone treatment reduces insulin sensitivity of HGP, induces a fasting-like phenotype in fed mice, and perturbs the fed-to-fasting transition...
  7. pmc Fenofibrate simultaneously induces hepatic fatty acid oxidation, synthesis, and elongation in mice
    Maaike H Oosterveer
    Department of Pediatrics, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands
    J Biol Chem 284:34036-44. 2009
    ..These observations may reflect a physiological mechanism by which PPARalpha and SREBP-1c collectively ensure proper handling of fatty acids to protect the liver against cytotoxic damage...
  8. pmc An increased flux through the glucose 6-phosphate pool in enterocytes delays glucose absorption in Fxr-/- mice
    Theo H van Dijk
    Departments of Laboratory Medicine and Pediatrics, Center for Liver Digestive and Metabolic Diseases, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands
    J Biol Chem 284:10315-23. 2009
    ..Thus, our results show involvement of FXR in intestinal glucose absorption, representing a novel physiological function for this nuclear receptor...
  9. doi Inhibition of mitochondrial fatty acid oxidation in vivo only slightly suppresses gluconeogenesis but enhances clearance of glucose in mice
    Terry G J Derks
    Department of Pediatrics, Laboratory of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
    Hepatology 47:1032-42. 2008
    ..Glucokinase and pyruvate kinase mRNA levels were significantly decreased, whereas pyruvate dehydrogenase kinase isozyme 4 expression was increased 30-fold; this suggested decreased glycolytic activity...
  10. doi Chronic prednisolone treatment aggravates hyperglycemia in mice fed a high-fat diet but does not worsen dietary fat-induced insulin resistance
    Anke J Laskewitz
    Department of Pediatrics, University of Groningen, University Medical Center Groningen, 9700 RB, Groningen, The Netherlands
    Endocrinology 153:3713-23. 2012
    ....
  11. ncbi Stimulation of lipogenesis by pharmacological activation of the liver X receptor leads to production of large, triglyceride-rich very low density lipoprotein particles
    Aldo Grefhorst
    Laboratory of Pediatrics, Center for Liver, Digestive and Metabolic Diseases, University Hospital Groningen, Hanzeplein 1, 9713 RB Groningen, The Netherlands
    J Biol Chem 277:34182-90. 2002
    ..We conclude that, in addition to raising high density lipoprotein cholesterol concentrations, pharmacological LXR activation in mice leads to development of hepatic steatosis and secretion of atherogenic, large TG-rich VLDL particles...
  12. ncbi Gene expression profiling in livers of mice after acute inhibition of beta-oxidation
    Feike R van der Leij
    Center for Liver, Digestive, and Metabolic Diseases, Laboratory of Pediatrics, University Medical Center Groningen, University of Groningen, CMCV, Groningen, The Netherlands
    Genomics 90:680-9. 2007
    ..Surprisingly, a strong reduction in the expression of genes involved in hepatic bile salt metabolism and transport was observed. Therefore, this transcriptome analysis opens new avenues for research...
  13. doi The liver X receptor: control of cellular lipid homeostasis and beyond Implications for drug design
    Maaike H Oosterveer
    Department of Pediatrics, Center for Liver Digestive and Metabolic Diseases, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
    Prog Lipid Res 49:343-52. 2010
    ..Finally, pathway analyses of LXR actions provide tools to evaluate and optimize the effectiveness of novel therapeutic strategies to prevent and/or treat metabolic diseases...
  14. doi Pharmacological LXR activation reduces presence of SR-B1 in liver membranes contributing to LXR-mediated induction of HDL-cholesterol
    Aldo Grefhorst
    Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
    Atherosclerosis 222:382-9. 2012
    ..Mechanisms underlying these LXR-mediated effects have not been fully elucidated...
  15. doi A systems biology approach reveals the physiological origin of hepatic steatosis induced by liver X receptor activation
    Brenda S Hijmans
    Departments of Pediatrics and Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands Netherlands Consortium for Systems Biology, University of Amsterdam, Amsterdam, The Netherlands Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands and Groningen Centre for Systems Biology, University of Groningen, Groningen, The Netherlands
    FASEB J 29:1153-64. 2015
    ..This study illustrates that complex effects of pharmacological intervention can be translated into distinct patterns of metabolic regulation through state-of-the-art mathematical modeling...
  16. doi Zonation of glucose and fatty acid metabolism in the liver: mechanism and metabolic consequences
    Brenda S Hijmans
    Departments of Pediatrics and Laboratory Medicine, University of Groningen, University Medical Center Groningen, The Netherlands Electronic address
    Biochimie 96:121-9. 2014
    ..Here we provide a theoretical framework to explain this so-called 'insulin signaling paradox' in the context of metabolic zonation of the liver...
  17. ncbi The farnesoid X receptor modulates adiposity and peripheral insulin sensitivity in mice
    Bertrand Cariou
    Institut Pasteur de Lille, Departement d Atherosclerose, Lille, F 59019, France
    J Biol Chem 281:11039-49. 2006
    ..This unexpected function of FXR opens new perspectives for the treatment of type 2 diabetes...
  18. ncbi Hepatic PCSK9 expression is regulated by nutritional status via insulin and sterol regulatory element-binding protein 1c
    Philippe Costet
    INSERM, U539, CHU Hotel Dieu, 44000, Nantes, France
    J Biol Chem 281:6211-8. 2006
    ..Together, these results show that PCSK9 expression is regulated by nutritional status and insulinemia...
  19. pmc Pharmacological inhibition of glucosylceramide synthase enhances insulin sensitivity
    Johannes M Aerts
    Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
    Diabetes 56:1341-9. 2007
    ....
  20. ncbi Transient impairment of the adaptive response to fasting in FXR-deficient mice
    Bertrand Cariou
    Research Unit 545 INSERM, Atherosclerosis Department, Pasteur Institute of Lille, Faculty of Pharmacy, Lille2 University, Lille, France
    FEBS Lett 579:4076-80. 2005
    ..Moreover, hepatic PEPCK gene expression was transiently lower in FXR-/- mice after 6h of fasting and was decreased in FXR-/- hepatocytes. FXR therefore plays an unexpected role in the control of fuel availability upon fasting...
  21. ncbi The farnesoid X receptor modulates hepatic carbohydrate metabolism during the fasting-refeeding transition
    Daniel Duran-Sandoval
    U R 545 INSERM, Atherosclerosis Department, Pasteur Institute of Lille and the Faculty of Pharmacy, Lille2 University, France
    J Biol Chem 280:29971-9. 2005
    ..Moreover, activated FXR interfered negatively with the carbohydrate response elements regions. These results identify a novel role for FXR as a modulator of hepatic carbohydrate metabolism...
  22. pmc Therapeutic RNAi targeting PCSK9 acutely lowers plasma cholesterol in rodents and LDL cholesterol in nonhuman primates
    Maria Frank-Kamenetsky
    Alnylam Pharmaceuticals, 300 Third Street, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 105:11915-20. 2008
    ..These results validate PCSK9 targeting with RNAi therapeutics as an approach to specifically lower LDLc, paving the way for the development of PCSK9-lowering agents as a future strategy for treatment of hypercholesterolemia...
  23. pmc Plasma PCSK9 preferentially reduces liver LDL receptors in mice
    Aldo Grefhorst
    Department of Molecular Genetics, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390 9046, USA
    J Lipid Res 49:1303-11. 2008
    ....