PMID- 32505735 OWN - NLM STAT- MEDLINE DCOM- 20210427 LR - 20240402 IS - 1878-7533 (Electronic) IS - 1550-7289 (Print) IS - 1550-7289 (Linking) VI - 16 IP - 9 DP - 2020 Sep TI - Effects of gastric bypass surgery on expression of glucose transporters and fibrotic biomarkers in kidney of diabetic fatty rats. PG - 1242-1248 LID - S1550-7289(20)30201-X [pii] LID - 10.1016/j.soard.2020.04.017 [doi] AB - BACKGROUND: Diabetic nephropathy is the leading cause of chronic kidney disease. Observational studies suggest Roux-en-Y gastric bypass (RYGB) reduces progression of diabetic nephropathy. OBJECTIVES: To unravel the mechanisms by which RYGB is beneficial and protective for diabetic nephropathy. SETTING: Academic laboratories. METHODS: Forty-eight Zucker diabetic fatty rats were randomized to RYGB, sham surgery (SHAM), or pair-fed (PF) groups. An oral glucose tolerance test was performed at 25 days post intervention and kidneys were harvested at 30 days. Primary outcome measures included expression of key genes and proteins in the glucose transport, oxidative stress, inflammation, and fibrosis pathways. RESULTS: Thirty days post intervention, RYGB rats weighed 349 +/- 8 g, which was lower than SHAM (436 +/- 14 g, P < .001), but not PF (374 +/- 18 g) rats. RYGB rats had lower fasting glucose than PF animals and improved homeostatic model assessment of insulin resistance compared with PF and SHAM groups. These enhanced metabolic outcomes were accompanied by reduced sodium-glucose co-transporter 1 (Sglt1) gene expression (-23% versus PF, P = .01) in the kidney of RYGB rats. Expression of Sglt2, Glut1, or Glut2 mRNA, or oxidative stress and inflammation markers did not differ significantly. However, RYGB surgery induced a 19% lower expression of transforming growth factor (Tgfbeta) mRNA (P = .004) compared with SHAM treated animals. Notably, adenosine monophosphate-activated protein kinase phosphorylation was increased (P = .04) in kidneys of the RYGB surgery animals. CONCLUSIONS: Improvement of hyperglycemia after RYGB may reduce the glucose load on the kidney leading to a downregulation of specific glucose transporters. RYGB surgery may also attenuate kidney fibrosis through the adenosine monophosphate-activated protein kinase/TGFbeta pathway. CI - Copyright (c) 2020 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved. FAU - Vangoitsenhoven, Roman AU - Vangoitsenhoven R AD - Bariatric and Metabolic Institute, Department of General Surgery, Cleveland Clinic, Cleveland, Ohio; Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium. FAU - Mulya, Anny AU - Mulya A AD - Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio. FAU - Mosinski, J David AU - Mosinski JD AD - Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio; Gannon University, Erie, Pennsylvania. FAU - Brethauer, Stacy A AU - Brethauer SA AD - Bariatric and Metabolic Institute, Department of General Surgery, Cleveland Clinic, Cleveland, Ohio; Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio. FAU - Schauer, Philip R AU - Schauer PR AD - Bariatric and Metabolic Institute, Department of General Surgery, Cleveland Clinic, Cleveland, Ohio; Pennington Biomedical Research Center, Baton Rouge, Louisiana. FAU - Kirwan, John P AU - Kirwan JP AD - Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio; Pennington Biomedical Research Center, Baton Rouge, Louisiana. FAU - Aminian, Ali AU - Aminian A AD - Bariatric and Metabolic Institute, Department of General Surgery, Cleveland Clinic, Cleveland, Ohio. Electronic address: aminiaa@ccf.org. LA - eng GR - R01 DK089547/DK/NIDDK NIH HHS/United States GR - U54 GM104940/GM/NIGMS NIH HHS/United States PT - Journal Article DEP - 20200424 PL - United States TA - Surg Obes Relat Dis JT - Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery JID - 101233161 RN - 0 (Biomarkers) RN - 0 (Blood Glucose) RN - 0 (Glucose Transport Proteins, Facilitative) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Animals MH - Biomarkers MH - Blood Glucose MH - *Diabetes Mellitus MH - Fibrosis MH - *Gastric Bypass MH - Glucose MH - Glucose Transport Proteins, Facilitative MH - Kidney MH - Rats MH - Rats, Zucker PMC - PMC8276306 MID - NIHMS1718894 OTO - NOTNLM OT - Bariatric surgery OT - Diabetes OT - Diabetic nephropathy OT - Gastric bypass OT - RYGB OT - Transforming growth factor OT - Weight loss COIS- Disclosure statement The authors have no conflicts of interest or financial ties to disclose. EDAT- 2020/06/09 06:00 MHDA- 2021/04/28 06:00 PMCR- 2021/07/13 CRDT- 2020/06/08 06:00 PHST- 2019/10/09 00:00 [received] PHST- 2020/03/31 00:00 [revised] PHST- 2020/04/12 00:00 [accepted] PHST- 2020/06/09 06:00 [pubmed] PHST- 2021/04/28 06:00 [medline] PHST- 2020/06/08 06:00 [entrez] PHST- 2021/07/13 00:00 [pmc-release] AID - S1550-7289(20)30201-X [pii] AID - 10.1016/j.soard.2020.04.017 [doi] PST - ppublish SO - Surg Obes Relat Dis. 2020 Sep;16(9):1242-1248. doi: 10.1016/j.soard.2020.04.017. Epub 2020 Apr 24.