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.

Bioscience Research and Early Development Cardiovascular Renal and Metabolism BioPharmaceuticals R and D AstraZeneca Gothenburg Sweden

Chair of Nutrition and Immunology Technische Universität München Freising Germany

Department of Clinical Physiology Sahlgrenska University Hospital Sweden

Department of Molecular and Clinical Medicine Wallenberg Laboratory Institute of Medicine University of Gothenburg Sweden

Department of Nutritional Physiology Technische Universität München Freising Germany

Department of Pathology University of Washington School of Medicine Seattle USA

Department of Renal Medicine Division of Medicine University College London UK

Department of Surgery Institute of Clinical Sciences Sahlgrenska Academy University of Gothenburg Gothenburg Sweden

Institute of Physiology Czech Academy of Sciences Prague Czech Republic

Wallenberg Centre for Molecular and Translational Medicine University of Gothenburg Sweden

000      

00000naa a2200000 a 4500

001      

bmc21011498

003      

CZ-PrNML

005      

20210507103431.0

007      

ta

008      

210420s2021 ne f 000 0|eng||

009      

AR

024    7_

$a 10.1016/j.lfs.2020.118974 $2 doi

035    __

$a (PubMed)33385407

040    __

$a ABA008 $b cze $d ABA008 $e AACR2

041    0_

$a eng

044    __

$a ne

100    1_

$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

245    10

$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

520    9_

$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.

650    _2

$a dospělí $7 D000328

650    _2

$a zvířata $7 D000818

650    _2

$a modely nemocí na zvířatech $7 D004195

650    _2

$a down regulace $7 D015536

650    _2

$a ženské pohlaví $7 D005260

650    _2

$a žaludeční bypass $7 D015390

650    _2

$a exprese genu $7 D015870

650    _2

$a lidé $7 D006801

650    _2

$a inzulin $x metabolismus $7 D007328

650    _2

$a inzulinová rezistence $7 D007333

650    _2

$a střevní sliznice $x metabolismus $7 D007413

650    _2

$a tenké střevo $x metabolismus $7 D007421

650    _2

$a jejunum $x metabolismus $7 D007583

650    _2

$a leptin $x nedostatek $x metabolismus $7 D020738

650    _2

$a mužské pohlaví $7 D008297

650    _2

$a myši $7 D051379

650    _2

$a myši inbrední C57BL $7 D008810

650    _2

$a lidé středního věku $7 D008875

650    _2

$a obezita $x genetika $x metabolismus $7 D009765

650    _2

$a protein - isoformy $7 D020033

650    _2

$a messenger RNA $x genetika $x metabolismus $7 D012333

650    _2

$a transportní proteiny pro sodík a glukosu $x biosyntéza $x genetika $x metabolismus $7 D051247

650    _2

$a transkriptom $7 D059467

650    _2

$a hmotnostní úbytek $7 D015431

655    _2

$a časopisecké články $7 D016428

700    1_

$a Casselbrant, Anna $u Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

700    1_

$a Rath, Eva $u Chair of Nutrition and Immunology, Technische Universität München, Freising, Germany

700    1_

$a Zietek, Tamara $u Department of Nutritional Physiology, Technische Universität München, Freising, Germany

700    1_

$a Strömstedt, Maria $u Bioscience, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden

700    1_

$a Adingupu, Damilola D $u Bioscience, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden

700    1_

$a Karlsson, Daniel $u Bioscience, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden

700    1_

$a Fritsch Fredin, Maria $u Bioscience, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden

700    1_

$a Ergang, Peter $u Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic

700    1_

$a Pácha, Jiří $u Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic

700    1_

$a Batorsky, Anna $u Department of Pathology, University of Washington School of Medicine, Seattle, USA

700    1_

$a Alpers, Charles E $u Department of Pathology, University of Washington School of Medicine, Seattle, USA

700    1_

$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

700    1_

$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

700    1_

$a Ericsson, Anette $u Bioscience, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden

700    1_

$a Björnson Granqvist, Anna $u Bioscience, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden

700    1_

$a Wallenius, Ville $u Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

700    1_

$a Fändriks, Lars $u Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

700    1_

$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

773    0_

$w MED00003147 $t Life sciences $x 1879-0631 $g Roč. 267, č. - (2021), s. 118974

856    41

$u https://pubmed.ncbi.nlm.nih.gov/33385407 $y Pubmed

910    __

$a ABA008 $b sig $c sign $y p $z 0

990    __

$a 20210420 $b ABA008

991    __

$a 20210507103430 $b ABA008

999    __

$a ok $b bmc $g 1650009 $s 1131877

BAS    __

$a 3

BAS    __

$a PreBMC

BMC    __

$a 2021 $b 267 $c - $d 118974 $e 20201230 $i 1879-0631 $m Life sciences $n Life Sci $x MED00003147

LZP    __

$a Pubmed-20210420