Acute retinol mobilization by retinol-binding protein 4 in mouse liver induces fibroblast growth factor 21 expression
Hepatocytes secrete retinol-binding protein 4 (RBP4) into circulation, thereby mobilizing vitamin A from the liver to provide retinol for extrahepatic tissues. Obesity and insulin resistance are associated with elevated RBP4 levels in the blood. However, in a previous study, we observed that chronic...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-10-01
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| Series: | Journal of Lipid Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227522001018 |
| _version_ | 1811272200412463104 |
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| author | Julia S. Steinhoff Carina Wagner Ulrike Taschler Sascha Wulff Marie F. Kiefer Konstantin M. Petricek Sylvia J. Wowro Moritz Oster Roberto E. Flores Na Yang Chen Li Yueming Meng Manuela Sommerfeld Stefan Weger Andrea Henze Jens Raila Achim Lass Michael Schupp |
| author_facet | Julia S. Steinhoff Carina Wagner Ulrike Taschler Sascha Wulff Marie F. Kiefer Konstantin M. Petricek Sylvia J. Wowro Moritz Oster Roberto E. Flores Na Yang Chen Li Yueming Meng Manuela Sommerfeld Stefan Weger Andrea Henze Jens Raila Achim Lass Michael Schupp |
| author_sort | Julia S. Steinhoff |
| collection | DOAJ |
| description | Hepatocytes secrete retinol-binding protein 4 (RBP4) into circulation, thereby mobilizing vitamin A from the liver to provide retinol for extrahepatic tissues. Obesity and insulin resistance are associated with elevated RBP4 levels in the blood. However, in a previous study, we observed that chronically increased RBP4 by forced Rbp4 expression in the liver does not impair glucose homeostasis in mice. Here, we investigated the effects of an acute mobilization of hepatic vitamin A stores by hepatic overexpression of RBP4 in mice. We show that hepatic retinol mobilization decreases body fat content and enhances fat turnover. Mechanistically, we found that acute retinol mobilization increases hepatic expression and serum levels of fibroblast growth factor 21 (FGF21), which is regulated by retinol mobilization and retinoic acid in primary hepatocytes. Moreover, we provide evidence that the insulin-sensitizing effect of FGF21 is associated with organ-specific adaptations in retinoid homeostasis. Taken together, our findings identify a novel crosstalk between retinoid homeostasis and FGF21 in mice with acute RBP4-mediated retinol mobilization from the liver. |
| first_indexed | 2024-04-12T22:34:41Z |
| format | Article |
| id | doaj.art-3e03abb6a7e44542a7029ef73356845c |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-04-12T22:34:41Z |
| publishDate | 2022-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-3e03abb6a7e44542a7029ef73356845c2022-12-22T03:13:52ZengElsevierJournal of Lipid Research0022-22752022-10-016310100268Acute retinol mobilization by retinol-binding protein 4 in mouse liver induces fibroblast growth factor 21 expressionJulia S. Steinhoff0Carina Wagner1Ulrike Taschler2Sascha Wulff3Marie F. Kiefer4Konstantin M. Petricek5Sylvia J. Wowro6Moritz Oster7Roberto E. Flores8Na Yang9Chen Li10Yueming Meng11Manuela Sommerfeld12Stefan Weger13Andrea Henze14Jens Raila15Achim Lass16Michael Schupp17Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Pharmacology, Berlin, GermanyInstitute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, AustriaInstitute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, AustriaCharité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Pharmacology, Berlin, GermanyCharité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Pharmacology, Berlin, GermanyCharité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Pharmacology, Berlin, GermanyCharité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Pharmacology, Berlin, GermanyCharité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Pharmacology, Berlin, GermanyCharité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Pharmacology, Berlin, GermanyCharité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Pharmacology, Berlin, GermanyCharité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Pharmacology, Berlin, GermanyCharité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Pharmacology, Berlin, GermanyCharité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Pharmacology, Berlin, GermanyCharité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Virology, Campus Benjamin Franklin, Berlin, GermanyMartin Luther University Halle-Wittenberg, Institute of Agricultural and Nutritional Sciences, Halle, Germany; Junior Research Group ProAID, Institute of Nutritional Science, University of Potsdam, Nuthetal, GermanyDepartment of Physiology and Pathophysiology, Institute of Nutritional Science, University of Potsdam, Nuthetal, GermanyInstitute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria; BioTechMed-Graz, Graz, AustriaCharité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Pharmacology, Berlin, Germany; For correspondence: Michael SchuppHepatocytes secrete retinol-binding protein 4 (RBP4) into circulation, thereby mobilizing vitamin A from the liver to provide retinol for extrahepatic tissues. Obesity and insulin resistance are associated with elevated RBP4 levels in the blood. However, in a previous study, we observed that chronically increased RBP4 by forced Rbp4 expression in the liver does not impair glucose homeostasis in mice. Here, we investigated the effects of an acute mobilization of hepatic vitamin A stores by hepatic overexpression of RBP4 in mice. We show that hepatic retinol mobilization decreases body fat content and enhances fat turnover. Mechanistically, we found that acute retinol mobilization increases hepatic expression and serum levels of fibroblast growth factor 21 (FGF21), which is regulated by retinol mobilization and retinoic acid in primary hepatocytes. Moreover, we provide evidence that the insulin-sensitizing effect of FGF21 is associated with organ-specific adaptations in retinoid homeostasis. Taken together, our findings identify a novel crosstalk between retinoid homeostasis and FGF21 in mice with acute RBP4-mediated retinol mobilization from the liver.http://www.sciencedirect.com/science/article/pii/S0022227522001018vitamin Aretinoidsglucosehepatic retinol mobilizationretinyl ester storageobesity |
| spellingShingle | Julia S. Steinhoff Carina Wagner Ulrike Taschler Sascha Wulff Marie F. Kiefer Konstantin M. Petricek Sylvia J. Wowro Moritz Oster Roberto E. Flores Na Yang Chen Li Yueming Meng Manuela Sommerfeld Stefan Weger Andrea Henze Jens Raila Achim Lass Michael Schupp Acute retinol mobilization by retinol-binding protein 4 in mouse liver induces fibroblast growth factor 21 expression Journal of Lipid Research vitamin A retinoids glucose hepatic retinol mobilization retinyl ester storage obesity |
| title | Acute retinol mobilization by retinol-binding protein 4 in mouse liver induces fibroblast growth factor 21 expression |
| title_full | Acute retinol mobilization by retinol-binding protein 4 in mouse liver induces fibroblast growth factor 21 expression |
| title_fullStr | Acute retinol mobilization by retinol-binding protein 4 in mouse liver induces fibroblast growth factor 21 expression |
| title_full_unstemmed | Acute retinol mobilization by retinol-binding protein 4 in mouse liver induces fibroblast growth factor 21 expression |
| title_short | Acute retinol mobilization by retinol-binding protein 4 in mouse liver induces fibroblast growth factor 21 expression |
| title_sort | acute retinol mobilization by retinol binding protein 4 in mouse liver induces fibroblast growth factor 21 expression |
| topic | vitamin A retinoids glucose hepatic retinol mobilization retinyl ester storage obesity |
| url | http://www.sciencedirect.com/science/article/pii/S0022227522001018 |
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