Ronja Fedders, Matthias Muenzner, Pamela Weber, Manuela Sommerfeld, Miriam Knauer, Sarah Kedziora, Naomi Kast, Steffi Heidenreich, Jens Raila, Stefan Weger, Andrea Henze, Michael Schupp
- Retinol-binding protein 4 (RBP4) is the major transport protein for retinol in blood. Recent evidence from genetic mouse models shows that circulating RBP4 derives exclusively from hepatocytes. Because RBP4 is elevated in obesity and associates with the development of glucose intolerance and insulin resistance, we tested whether a liver-specific overexpression of RBP4 in mice impairs glucose homeostasis. We used adeno-associated viruses (AAV) that contain a highly liver-specific promoter to drive expression of murine RBP4 in livers of adult mice. The resulting increase in serum RBP4 levels in these mice was comparable with elevated levels that were reported in obesity. Surprisingly, we found that increasing circulating RBP4 had no effect on glucose homeostasis. Also during a high-fat diet challenge, elevated levels of RBP4 in the circulation failed to aggravate the worsening of systemic parameters of glucose and energy homeostasis. These findings show that liver-secreted RBP4 does not impair glucose homeostasis. We conclude that aRetinol-binding protein 4 (RBP4) is the major transport protein for retinol in blood. Recent evidence from genetic mouse models shows that circulating RBP4 derives exclusively from hepatocytes. Because RBP4 is elevated in obesity and associates with the development of glucose intolerance and insulin resistance, we tested whether a liver-specific overexpression of RBP4 in mice impairs glucose homeostasis. We used adeno-associated viruses (AAV) that contain a highly liver-specific promoter to drive expression of murine RBP4 in livers of adult mice. The resulting increase in serum RBP4 levels in these mice was comparable with elevated levels that were reported in obesity. Surprisingly, we found that increasing circulating RBP4 had no effect on glucose homeostasis. Also during a high-fat diet challenge, elevated levels of RBP4 in the circulation failed to aggravate the worsening of systemic parameters of glucose and energy homeostasis. These findings show that liver-secreted RBP4 does not impair glucose homeostasis. We conclude that a modest increase of its circulating levels in mice, as observed in the obese, insulin-resistant state, is unlikely to be a causative factor for impaired glucose homeostasis.…
MetadatenAuthor details: | Ronja Fedders, Matthias Muenzner, Pamela Weber, Manuela Sommerfeld, Miriam Knauer, Sarah Kedziora, Naomi Kast, Steffi Heidenreich, Jens RailaORCiDGND, Stefan Weger, Andrea HenzeORCiDGND, Michael Schupp |
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DOI: | https://doi.org/10.1074/jbc.RA118.004294 |
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ISSN: | 1083-351X |
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Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/30126844 |
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Title of parent work (English): | The journal of biological chemistry |
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Publisher: | American Society for Biochemistry and Molecular Biology |
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Place of publishing: | Bethesda |
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Publication type: | Article |
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Language: | English |
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Date of first publication: | 2018/07/20 |
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Publication year: | 2021 |
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Release date: | 2021/09/24 |
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Tag: | TTR; glucose metabolism; insulin resistance; liver; mouse; retinoid-binding protein |
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Volume: | 293 |
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Issue: | 39 |
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Number of pages: | 8 |
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First page: | 15269 |
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Last Page: | 15276 |
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Funding institution: | German Research Foundation (Deutsche Forschungsgemeinschaft)German Research Foundation (DFG) [SCHU 2546/1-1, SCHU 2546/5-1]; European UnionEuropean Union (EU) [CIG 291867] |
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Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Biochemie und Biologie |
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DDC classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
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Peer review: | Referiert |
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Publishing method: | Open Access / Bronze Open-Access |
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License (German): | CC-BY - Namensnennung 4.0 International |
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