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Intestinal sodium/glucose cotransporter 3 expression is epithelial and downregulated in obesity

M. Soták, A. Casselbrant, E. Rath, T. Zietek, M. Strömstedt, DD. Adingupu, D. Karlsson, M. Fritsch Fredin, P. Ergang, J. Pácha, A. Batorsky, CE. Alpers, E. Börgeson, PBL. Hansen, A. Ericsson, A. Björnson Granqvist, V. Wallenius, L. Fändriks, RJ. Unwin

. 2021 ; 267 (-) : 118974. [pub] 20201230

Language English Country Netherlands

Document type Journal Article

Persistent link   https://www.medvik.cz/link/bmc21011498

AIM: We aimed to determine whether the sodium/glucose cotransporter family member SGLT3, a proposed glucose sensor, is expressed in the intestine and/or kidney, and if its expression is altered in mouse models of obesity and in humans before and after weight-loss surgery. MAIN METHODS: We used in-situ hybridization and quantitative PCR to determine whether the Sglt3 isoforms 3a and 3b were expressed in the intestine and kidney of C57, leptin-deficient ob/ob, and diabetic BTBR ob/ob mice. Western blotting and immunohistochemistry were also used to assess SGLT3 protein levels in jejunal biopsies from obese patients before and after weight-loss Roux-en-Y gastric bypass surgery (RYGB), and in lean healthy controls. KEY FINDINGS: Sglt3a/3b mRNA was detected in the small intestine (duodenum, jejunum and ileum), but not in the large intestine or kidneys of mice. Both isoforms were detected in epithelial cells (confirmed using intestinal organoids). Expression of Sglt3a/3b mRNA in duodenum and jejunum was significantly lower in ob/ob and BTBR ob/ob mice than in normal-weight littermates. Jejunal SGLT3 protein levels in aged obese patients before RYGB were lower than in lean individuals, but substantially upregulated 6 months post-RYGB. SIGNIFICANCE: Our study shows that Sglt3a/3b is expressed primarily in epithelial cells of the small intestine in mice. Furthermore, we observed an association between intestinal mRNA Sglt3a/3b expression and obesity in mice, and between jejunal SGLT3 protein levels and obesity in humans. Further studies are required to determine the possible role of SGLT3 in obesity.

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$a Soták, Matúš $u Bioscience, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden; Department of Molecular and Clinical Medicine, Wallenberg Laboratory, Institute of Medicine, University of Gothenburg, Sweden; Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Sweden. Electronic address: matus@sotak.info
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$a Intestinal sodium/glucose cotransporter 3 expression is epithelial and downregulated in obesity / $c M. Soták, A. Casselbrant, E. Rath, T. Zietek, M. Strömstedt, DD. Adingupu, D. Karlsson, M. Fritsch Fredin, P. Ergang, J. Pácha, A. Batorsky, CE. Alpers, E. Börgeson, PBL. Hansen, A. Ericsson, A. Björnson Granqvist, V. Wallenius, L. Fändriks, RJ. Unwin
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$a AIM: We aimed to determine whether the sodium/glucose cotransporter family member SGLT3, a proposed glucose sensor, is expressed in the intestine and/or kidney, and if its expression is altered in mouse models of obesity and in humans before and after weight-loss surgery. MAIN METHODS: We used in-situ hybridization and quantitative PCR to determine whether the Sglt3 isoforms 3a and 3b were expressed in the intestine and kidney of C57, leptin-deficient ob/ob, and diabetic BTBR ob/ob mice. Western blotting and immunohistochemistry were also used to assess SGLT3 protein levels in jejunal biopsies from obese patients before and after weight-loss Roux-en-Y gastric bypass surgery (RYGB), and in lean healthy controls. KEY FINDINGS: Sglt3a/3b mRNA was detected in the small intestine (duodenum, jejunum and ileum), but not in the large intestine or kidneys of mice. Both isoforms were detected in epithelial cells (confirmed using intestinal organoids). Expression of Sglt3a/3b mRNA in duodenum and jejunum was significantly lower in ob/ob and BTBR ob/ob mice than in normal-weight littermates. Jejunal SGLT3 protein levels in aged obese patients before RYGB were lower than in lean individuals, but substantially upregulated 6 months post-RYGB. SIGNIFICANCE: Our study shows that Sglt3a/3b is expressed primarily in epithelial cells of the small intestine in mice. Furthermore, we observed an association between intestinal mRNA Sglt3a/3b expression and obesity in mice, and between jejunal SGLT3 protein levels and obesity in humans. Further studies are required to determine the possible role of SGLT3 in obesity.
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$a Casselbrant, Anna $u Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
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$a Rath, Eva $u Chair of Nutrition and Immunology, Technische Universität München, Freising, Germany
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$a Zietek, Tamara $u Department of Nutritional Physiology, Technische Universität München, Freising, Germany
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$a Strömstedt, Maria $u Bioscience, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
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$a Adingupu, Damilola D $u Bioscience, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
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$a Karlsson, Daniel $u Bioscience, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
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$a Fritsch Fredin, Maria $u Bioscience, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
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$a Ergang, Peter $u Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic
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$a Pácha, Jiří $u Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic
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$a Batorsky, Anna $u Department of Pathology, University of Washington School of Medicine, Seattle, USA
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$a Alpers, Charles E $u Department of Pathology, University of Washington School of Medicine, Seattle, USA
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$a Börgeson, Emma $u Department of Molecular and Clinical Medicine, Wallenberg Laboratory, Institute of Medicine, University of Gothenburg, Sweden; Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Sweden; Department of Clinical Physiology, Sahlgrenska University Hospital, Sweden
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$a Hansen, Pernille B L $u Bioscience, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden; Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Sweden
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$a Ericsson, Anette $u Bioscience, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
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$a Björnson Granqvist, Anna $u Bioscience, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
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$a Wallenius, Ville $u Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
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$a Fändriks, Lars $u Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
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$a Unwin, Robert J $u Bioscience, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden; Department of Renal Medicine, Division of Medicine, University College London, UK
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