Search

Your search keyword '"Ramos Pittol, José M"' showing total 21 results
Start Over Author "Ramos Pittol, José M"
21 results on '"Ramos Pittol, José M"'

4. Ablation of liver Fxr results in an increased colonic mucus barrier in mice.

Author

dI&I I&I-2, Dep Biomolecular Health Sciences, Pathobiologie, dPB RMSC, Ijssennagger, Noortje, van Rooijen, Kristel S., Magnúsdóttir, Stefanía, Ramos Pittol, José M., Willemsen, Ellen C.L., de Zoete, Marcel R., Baars, Matthijs J.D., Stege, Paul B., Colliva, Carolina, Pellicciari, Roberto, Youssef, Sameh A., de Bruin, Alain, Vercoulen, Yvonne, Kuipers, Folkert, van Mil, Saskia W.C., dI&I I&I-2, Dep Biomolecular Health Sciences, Pathobiologie, dPB RMSC, Ijssennagger, Noortje, van Rooijen, Kristel S., Magnúsdóttir, Stefanía, Ramos Pittol, José M., Willemsen, Ellen C.L., de Zoete, Marcel R., Baars, Matthijs J.D., Stege, Paul B., Colliva, Carolina, Pellicciari, Roberto, Youssef, Sameh A., de Bruin, Alain, Vercoulen, Yvonne, Kuipers, Folkert, and van Mil, Saskia W.C.

Published
2021

5. Ablation of liver Fxr results in an increased colonic mucus barrier in mice

Author

CMM Groep Van Mil, Cancer, DBG Metabole en Endocriene Ziekten, MMB Research line 2, Infection & Immunity, CMM Groep Vercoulen, CMM, Child Health, Ijssennagger, Noortje, van Rooijen, Kristel S., Magnúsdóttir, Stefanía, Ramos Pittol, José M., Willemsen, Ellen C.L., de Zoete, Marcel R., Baars, Matthijs J.D., Stege, Paul B., Colliva, Carolina, Pellicciari, Roberto, Youssef, Sameh A., de Bruin, Alain, Vercoulen, Yvonne, Kuipers, Folkert, van Mil, Saskia W.C., CMM Groep Van Mil, Cancer, DBG Metabole en Endocriene Ziekten, MMB Research line 2, Infection & Immunity, CMM Groep Vercoulen, CMM, Child Health, Ijssennagger, Noortje, van Rooijen, Kristel S., Magnúsdóttir, Stefanía, Ramos Pittol, José M., Willemsen, Ellen C.L., de Zoete, Marcel R., Baars, Matthijs J.D., Stege, Paul B., Colliva, Carolina, Pellicciari, Roberto, Youssef, Sameh A., de Bruin, Alain, Vercoulen, Yvonne, Kuipers, Folkert, and van Mil, Saskia W.C.

Published
2021

6. Steroidogenic control of liver metabolism through a nuclear receptor-network

Author

Milona, Alexandra, Massafra, Vittoria, Vos, Harmjan, Naik, Jyoti, Artigas, Natalia, Paterson, Helen A.B., Bijsmans, Ingrid T.G.W., Willemsen, Ellen C.L., Ramos Pittol, Jose M., Miguel-Aliaga, Irene, Bosma, Piter, Burgering, Boudewijn M.T., Williamson, Catherine, Vernia, Santiago, Dhillo, Waljit S., van Mil, Saskia W.C., and Owen, Bryn M.

Published
2019
Full Text
View/download PDF

7. Farnesoid X Receptor Activation Promotes Hepatic Amino Acid Catabolism and Ammonium Clearance in Mice

Author

Massafra, Vittoria, Milona, Alexandra, Vos, Harmjan R, Ramos, Rúben J J, Gerrits, Johan, Willemsen, Ellen C L, Ramos Pittol, José M, Ijssennagger, Noortje, Houweling, Martin, Prinsen, Hubertus C M T, Verhoeven-Duif, Nanda M, Burgering, Boudewijn M T, van Mil, Saskia W C, dB&C FR-RMSC FR, and dB&C FR-RMSC FR

Subjects
Male, 0301 basic medicine, Glutamine Synthetase, Proteome, Cytoplasmic and Nuclear, Glutamine, Wistar, Gene Expression, Receptors, Cytoplasmic and Nuclear, Inbred C57BL, Mice, chemistry.chemical_compound, INT-747, Chenodeoxycholic acid, Receptors, Urea, Mice, Knockout, Bile acid, Gastroenterology, Obeticholic acid, Liver Proteome, Liver, Biochemistry, Urea cycle, Metabolome, Dietary Proteins, medicine.medical_specialty, medicine.drug_class, Knockout, Cps1, Biology, Chenodeoxycholic Acid, Bile Acids and Salts, 03 medical and health sciences, Ammonia, Internal medicine, medicine, Journal Article, Animals, Rats, Wistar, Liver X receptor, Hepatology, Catabolism, Rats, Mice, Inbred C57BL, 030104 developmental biology, Endocrinology, chemistry, Hepatocytes, Farnesoid X receptor
Abstract

Background & Aims The nuclear receptor subfamily 1 group H member 4 (NR1H4 or farnesoid X receptor [FXR]) regulates bile acid synthesis, transport, and catabolism. FXR also regulates postprandial lipid and glucose metabolism. We performed quantitative proteomic analyses of liver tissues from mice to evaluate these functions and investigate whether FXR regulates amino acid metabolism. Methods To study the role of FXR in mouse liver, we used mice with a disruption of Nr1h4 (FXR-knockout mice) and compared them with floxed control mice. Mice were gavaged with the FXR agonist obeticholic acid or vehicle for 11 days. Proteome analyses, as well as targeted metabolomics and chromatin immunoprecipitation, were performed on the livers of these mice. Primary rat hepatocytes were used to validate the role of FXR in amino acid catabolism by gene expression and metabolomics studies. Finally, control mice and mice with liver-specific disruption of Nr1h4 (liver FXR-knockout mice) were re-fed with a high-protein diet after 6 hours fasting and gavaged a 15 NH 4 Cl tracer. Gene expression and the metabolome were studied in the livers and plasma from these mice. Results In livers of control mice and primary rat hepatocytes, activation of FXR with obeticholic acid increased expression of proteins that regulate amino acid degradation, ureagenesis, and glutamine synthesis. We found FXR to bind to regulatory sites of genes encoding these proteins in control livers. Liver tissues from FXR-knockout mice had reduced expression of urea cycle proteins, and accumulated precursors of ureagenesis, compared with control mice. In liver FXR-knockout mice on a high-protein diet, the plasma concentration of newly formed urea was significantly decreased compared with controls. In addition, liver FXR-knockout mice had reduced hepatic expression of enzymes that regulate ammonium detoxification compared with controls. In contrast, obeticholic acid increased expression of genes encoding enzymes involved in ureagenesis compared with vehicle in C57Bl/6 mice. Conclusions In livers of mice, FXR regulates amino acid catabolism and detoxification of ammonium via ureagenesis and glutamine synthesis. Failure of the urea cycle and hyperammonemia are common in patients with acute and chronic liver diseases; compounds that activate FXR might promote ammonium clearance in these patients.

Published
2017

8. Characterization of stem cell-derived liver and intestinal organoids as a model system to study nuclear receptor biology

Author

Bijsmans, Ingrid T.G.W., Milona, Alexandra, Ijssennagger, Noortje, Willemsen, Ellen C.L., Ramos Pittol, José M., Jonker, Johan W., Lange, Katja, Hooiveld, Guido J.E.J., Mil, Saskia W.C., van, Bijsmans, Ingrid T.G.W., Milona, Alexandra, Ijssennagger, Noortje, Willemsen, Ellen C.L., Ramos Pittol, José M., Jonker, Johan W., Lange, Katja, Hooiveld, Guido J.E.J., and Mil, Saskia W.C., van

Abstract

Nuclear receptors (NRs) are ligand-activated transcription factors regulating a large variety of processes involved in reproduction, development, and metabolism. NRs are ideal drug targets because they are activated by lipophilic ligands that easily pass cell membranes. Immortalized cell lines recapitulate NR biology poorly and generating primary cultures is laborious and requires a constant need for donor material. There is a clear need for development of novel preclinical model systems that better resemble human physiology. Uncertainty due to technical limitations early in drug development is often the cause of preclinical drugs not reaching the clinic. Here, we studied whether organoids, mini-organs derived from the respective mouse tissue's stem cells, can serve as a novel model system to study NR biology and targetability. We characterized mRNA expression profiles of the NR superfamily in mouse liver, ileum, and colon organoids. Tissue-specific expression patterns were largely maintained in the organoids, indicating their suitability for NR research. Metabolic NRs Fxrα, Lxrα, Lxrβ, Pparα, and Pparγ induced expression of and binding to endogenous target genes. Transcriptome analyses of wildtype colon organoids stimulated with Rosiglitazone showed that lipid metabolism was the highest significant changed function, greatly mimicking the PPARs and Rosiglitazone function in vivo. Finally, using organoids we identify Trpm6, Slc26a3, Ang1, and Rnase4, as novel Fxr target genes. Our results demonstrate that organoids represent a framework to study NR biology that can be further expanded to human organoids to improve preclinical testing of novel drugs that target this pharmacologically important class of ligand activated transcription factors.

Published
2017

9. Farnesoid X Receptor Activation Promotes Hepatic Amino Acid Catabolism and Ammonium Clearance in Mice

Author

dB&C FR-RMSC FR, Massafra, Vittoria, Milona, Alexandra, Vos, Harmjan R, Ramos, Rúben J J, Gerrits, Johan, Willemsen, Ellen C L, Ramos Pittol, José M, Ijssennagger, Noortje, Houweling, Martin, Prinsen, Hubertus C M T, Verhoeven-Duif, Nanda M, Burgering, Boudewijn M T, van Mil, Saskia W C, dB&C FR-RMSC FR, Massafra, Vittoria, Milona, Alexandra, Vos, Harmjan R, Ramos, Rúben J J, Gerrits, Johan, Willemsen, Ellen C L, Ramos Pittol, José M, Ijssennagger, Noortje, Houweling, Martin, Prinsen, Hubertus C M T, Verhoeven-Duif, Nanda M, Burgering, Boudewijn M T, and van Mil, Saskia W C

Published
2017

10. Farnesoid X Receptor Activation Promotes Hepatic Amino Acid Catabolism and Ammonium Clearance in Mice

Author

CMM, CMM Groep Van Mil, Child Health, CMM Groep Burgering, Cancer, Genetica Sectie Metabole Diagnostiek, Genetica, Massafra, Vittoria, Milona, Alexandra, Vos, Harmjan R., Ramos, Rúben J J, Gerrits, Johan, Willemsen, Ellen C.L., Ramos Pittol, José M., Ijssennagger, Noortje, Houweling, Martin, Prinsen, Hubertus C.M.T., Verhoeven-Duif, Nanda M., Burgering, Boudewijn M.T., van Mil, Saskia W.C., CMM, CMM Groep Van Mil, Child Health, CMM Groep Burgering, Cancer, Genetica Sectie Metabole Diagnostiek, Genetica, Massafra, Vittoria, Milona, Alexandra, Vos, Harmjan R., Ramos, Rúben J J, Gerrits, Johan, Willemsen, Ellen C.L., Ramos Pittol, José M., Ijssennagger, Noortje, Houweling, Martin, Prinsen, Hubertus C.M.T., Verhoeven-Duif, Nanda M., Burgering, Boudewijn M.T., and van Mil, Saskia W.C.

Published
2017

11. Gene expression profiling in human precision cut liver slices in response to the FXR agonist obeticholic acid

Author

Ijssennagger, Noortje, Janssen, Aafke W F, Milona, Alexandra, Ramos Pittol, José M, Hollman, Danielle A A, Mokry, Michal, Betzel, Bark, Berends, Frits J, Janssen, Ignace M, van Mil, Saskia W C, and Kersten, Sander

Subjects
Human liver slices, Farnesoid X receptor, Research Support, Non-U.S. Gov't, Obeticholic acid, Journal Article, Gene expression profiling
Abstract

BACKGROUND & AIMS: The bile acid-activated farnesoid X receptor (FXR) is a nuclear receptor regulating bile acid, glucose and cholesterol homeostasis. Obeticholic acid (OCA), a promising drug for the treatment of non-alcoholic steatohepatitis (NASH) and type 2 diabetes, activates FXR. Mouse studies demonstrated that FXR activation by OCA alters hepatic expression of many genes. However, no data are available on the effects of OCA in the human liver. Here we generated gene expression profiles in human precision cut liver slices (hPCLS) after treatment with OCA. METHODS: hPCLS were incubated with OCA for 24h. Wild-type or FXR(-/-) mice received OCA or vehicle by oral gavage for 7days. RESULTS: Transcriptomic analysis showed that well-known FXR target genes, including NR0B2 (SHP), ABCB11 (BSEP), SLC51A (OSTα) and SLC51B (OSTβ), and ABCB4 (MDR3) are regulated by OCA in hPCLS. Ingenuity pathway analysis confirmed that 'FXR/RXR activation' is the most significantly changed pathway upon OCA treatment. Comparison of gene expression profiles in hPCLS and mouse livers identified 18 common potential FXR targets. ChIP-sequencing in mouse liver confirmed FXR binding to IR1 sequences of Akap13, Cgnl1, Dyrk3, Pdia5, Ppp1r3b and Tbx6. CONCLUSIONS: Our study shows that hPCLS respond to OCA treatment by upregulating well-known FXR target genes, demonstrating its suitability to study FXR-mediated gene regulation. We identified six novel bona-fide FXR target genes in both mouse and human liver. Finally, we discuss a possible explanation for changes in high or low density lipoprotein observed in NASH and primary biliary cholangitis patients treated with OCA based on the genomic expression profile in hPCLS.

Published
2016

13. Splenic dendritic cell involvement in FXR-mediated amelioration of DSS colitis

Author

Massafra, Vittoria, Ijssennagger, Noortje, Plantinga, Maud, Milona, Alexandra, Ramos Pittol, José M., Boes, Marianne, van Mil, Saskia W C, Massafra, Vittoria, Ijssennagger, Noortje, Plantinga, Maud, Milona, Alexandra, Ramos Pittol, José M., Boes, Marianne, and van Mil, Saskia W C

Published
2016

14. Gene expression profiling in human precision cut liver slices in response to the FXR agonist obeticholic acid

Author

CMM Groep Van Mil, MDL onderzoek 3, Child Health, Cancer, Ijssennagger, Noortje, Janssen, Aafke W F, Milona, Alexandra, Ramos Pittol, José M, Hollman, Danielle A A, Mokry, Michal, Betzel, Bark, Berends, Frits J, Janssen, Ignace M, van Mil, Saskia W C, Kersten, Sander, CMM Groep Van Mil, MDL onderzoek 3, Child Health, Cancer, Ijssennagger, Noortje, Janssen, Aafke W F, Milona, Alexandra, Ramos Pittol, José M, Hollman, Danielle A A, Mokry, Michal, Betzel, Bark, Berends, Frits J, Janssen, Ignace M, van Mil, Saskia W C, and Kersten, Sander

Published
2016

15. Splenic dendritic cell involvement in FXR-mediated amelioration of DSS colitis

Author

UMC Utrecht, CMM Groep Van Mil, Cancer, CTI Nierkens, Infection & Immunity, Immuno/reuma onderzoek 2 (Boes), Child Health, CTI Boes, Massafra, Vittoria, Ijssennagger, Noortje, Plantinga, Maud, Milona, Alexandra, Ramos Pittol, José M., Boes, Marianne, van Mil, Saskia W C, UMC Utrecht, CMM Groep Van Mil, Cancer, CTI Nierkens, Infection & Immunity, Immuno/reuma onderzoek 2 (Boes), Child Health, CTI Boes, Massafra, Vittoria, Ijssennagger, Noortje, Plantinga, Maud, Milona, Alexandra, Ramos Pittol, José M., Boes, Marianne, and van Mil, Saskia W C

Published
2016

16. Gene expression profiling in human precision cut liver slices in response to the FXR agonist obeticholic acid

Author

Ijssennagger, Noortje, primary, Janssen, Aafke W.F., additional, Milona, Alexandra, additional, Ramos Pittol, José M., additional, Hollman, Danielle A.A., additional, Mokry, Michal, additional, Betzel, Bark, additional, Berends, Frits J., additional, Janssen, Ignace M., additional, van Mil, Saskia W.C., additional, and Kersten, Sander, additional

Published
2016
Full Text
View/download PDF

18. The glucocorticoid mometasone furoate is a novel FXR ligand that decreases inflammatory but not metabolic gene expression

Author

Bijsmans, Ingrid T G W, Guercini, Chiara, Ramos Pittol, José M., Omta, Wienand, Milona, Alexandra, Lelieveld, Daphne, Egan, David A., Pellicciari, Roberto, Gioiello, Antimo, van Mil, Saskia W C, Bijsmans, Ingrid T G W, Guercini, Chiara, Ramos Pittol, José M., Omta, Wienand, Milona, Alexandra, Lelieveld, Daphne, Egan, David A., Pellicciari, Roberto, Gioiello, Antimo, and van Mil, Saskia W C

Published
2015

19. The glucocorticoid mometasone furoate is a novel FXR ligand that decreases inflammatory but not metabolic gene expression

Author

CMM Groep Van Mil, UMC Utrecht, CMM Sectie Celbiologie, CMM Cell Screening Center, Cancer, Child Health, Bijsmans, Ingrid T G W, Guercini, Chiara, Ramos Pittol, José M., Omta, Wienand, Milona, Alexandra, Lelieveld, Daphne, Egan, David A., Pellicciari, Roberto, Gioiello, Antimo, van Mil, Saskia W C, CMM Groep Van Mil, UMC Utrecht, CMM Sectie Celbiologie, CMM Cell Screening Center, Cancer, Child Health, Bijsmans, Ingrid T G W, Guercini, Chiara, Ramos Pittol, José M., Omta, Wienand, Milona, Alexandra, Lelieveld, Daphne, Egan, David A., Pellicciari, Roberto, Gioiello, Antimo, and van Mil, Saskia W C

Published
2015

21. Farnesoid X Receptor Activation Promotes Hepatic Amino Acid Catabolism and Ammonium Clearance in Mice.

Author

Massafra V, Milona A, Vos HR, Ramos RJJ, Gerrits J, Willemsen ECL, Ramos Pittol JM, Ijssennagger N, Houweling M, Prinsen HCMT, Verhoeven-Duif NM, Burgering BMT, and van Mil SWC

Subjects
Animals, Bile Acids and Salts metabolism, Chenodeoxycholic Acid analogs & derivatives, Chenodeoxycholic Acid pharmacology, Dietary Proteins administration & dosage, Gene Expression, Hepatocytes, Liver enzymology, Male, Metabolome, Mice, Mice, Inbred C57BL, Mice, Knockout, Proteome, Rats, Rats, Wistar, Receptors, Cytoplasmic and Nuclear antagonists & inhibitors, Ammonia metabolism, Glutamine biosynthesis, Liver metabolism, Receptors, Cytoplasmic and Nuclear genetics, Receptors, Cytoplasmic and Nuclear metabolism, Urea metabolism
Abstract

Background & Aims: The nuclear receptor subfamily 1 group H member 4 (NR1H4 or farnesoid X receptor [FXR]) regulates bile acid synthesis, transport, and catabolism. FXR also regulates postprandial lipid and glucose metabolism. We performed quantitative proteomic analyses of liver tissues from mice to evaluate these functions and investigate whether FXR regulates amino acid metabolism., Methods: To study the role of FXR in mouse liver, we used mice with a disruption of Nr1h4 (FXR-knockout mice) and compared them with floxed control mice. Mice were gavaged with the FXR agonist obeticholic acid or vehicle for 11 days. Proteome analyses, as well as targeted metabolomics and chromatin immunoprecipitation, were performed on the livers of these mice. Primary rat hepatocytes were used to validate the role of FXR in amino acid catabolism by gene expression and metabolomics studies. Finally, control mice and mice with liver-specific disruption of Nr1h4 (liver FXR-knockout mice) were re-fed with a high-protein diet after 6 hours fasting and gavaged a 15 NH 4 Cl tracer. Gene expression and the metabolome were studied in the livers and plasma from these mice., Results: In livers of control mice and primary rat hepatocytes, activation of FXR with obeticholic acid increased expression of proteins that regulate amino acid degradation, ureagenesis, and glutamine synthesis. We found FXR to bind to regulatory sites of genes encoding these proteins in control livers. Liver tissues from FXR-knockout mice had reduced expression of urea cycle proteins, and accumulated precursors of ureagenesis, compared with control mice. In liver FXR-knockout mice on a high-protein diet, the plasma concentration of newly formed urea was significantly decreased compared with controls. In addition, liver FXR-knockout mice had reduced hepatic expression of enzymes that regulate ammonium detoxification compared with controls. In contrast, obeticholic acid increased expression of genes encoding enzymes involved in ureagenesis compared with vehicle in C57Bl/6 mice., Conclusions: In livers of mice, FXR regulates amino acid catabolism and detoxification of ammonium via ureagenesis and glutamine synthesis. Failure of the urea cycle and hyperammonemia are common in patients with acute and chronic liver diseases; compounds that activate FXR might promote ammonium clearance in these patients., (Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Published
2017
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results