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.
Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Life Sci. 2021 Feb 15;267:118974. doi: 10.1016/j.lfs.2020.118974. Epub 2020 Dec 30.
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.
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.
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.
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.
我们旨在确定钠/葡萄糖协同转运蛋白家族成员 SGLT3 是否在肠道和/或肾脏中表达，以及其在肥胖小鼠模型和减肥手术前后的人类中是否表达改变。
我们使用原位杂交和定量 PCR 来确定 Sglt3 同工型 3a 和 3b 是否在 C57、瘦素缺乏型 ob/ob 和糖尿病 BTBR ob/ob 小鼠的肠道和肾脏中表达。还使用 Western 印迹和免疫组织化学来评估肥胖患者减肥 Roux-en-Y 胃旁路手术（RYGB）前后的空肠活检中的 SGLT3 蛋白水平，以及瘦健康对照者。
Sglt3a/3b mRNA 在小肠（十二指肠、空肠和回肠）中检测到，但在大肠或肾脏中未检测到。两种同工型均在肠类器官中确认的上皮细胞中检测到。ob/ob 和 BTBR ob/ob 小鼠的十二指肠和空肠 Sglt3a/3b mRNA 表达明显低于正常体重同窝仔鼠。RYGB 前年龄肥胖患者的空肠 SGLT3 蛋白水平低于瘦个体，但 RYGB 后 6 个月显著上调。
我们的研究表明，Sglt3a/3b 主要在小鼠的小肠上皮细胞中表达。此外，我们观察到小鼠肠道 Sglt3a/3b 表达与肥胖之间存在关联，以及人类空肠 SGLT3 蛋白水平与肥胖之间存在关联。需要进一步研究来确定 SGLT3 在肥胖中的可能作用。
