Abstract: FR-PO587

Gastric Bypass versus “Medical Bypass” – Impact on Experimental Diabetic Kidney Disease

Session Information

Category: Diabetes

  • 501 Diabetes Mellitus and Obesity: Basic - Experimental

Authors

  • Nair, Meera, University College Dublin, Dublin, Ireland
  • Canney, Aoife L, University College Dublin, Dublin, Ireland
  • Elliott, Jessie A, St. James''s Hospital, Dublin, Dublin 8, Ireland
  • fearon, naomi m, University College Dublin, Dublin, Ireland
  • Casselbrant, Anna, University of Gothenburg, Gothenburg, Sweden
  • Fandriks, Lars, University of Gothenburg, Gothenburg, Sweden
  • Le roux, Carel W, University College Dublin, Dublin, Ireland
  • Docherty, Neil G., University College Dublin, Dublin, Ireland
Background

Reductions in albuminuria are reported after Roux-en-Y gastric bypass (RYGB). Herein, we assess the impact of RYGB on podocyte injury in the Zucker Diabetic Fatty (ZDF) rat model of diabetic kidney disease (DKD) and compare glomerular injury and global renal transcriptomic responses of RYGB and matched ‘‘Medical Bypass’’(MB).

Methods

Study 1: Adult male ZDF rats underwent sham surgery (n=8) or RYGB (n=7). Study 2: Adult ZDF rats underwent sham surgery (n=15) or RYGB (n=9). Nine sham-operated rats were calorie restricted and received insulin, liraglutide, metformin, ramipril, rosuvastatin and fenofibrate for 2 months (MB). Zucker Fa/+ rats acted as healthy controls throughout. Bodyweight, glycaemia, albuminuria and glomerular injury specifically podocyte number, density and ultrastructure were assessed at follow up. Renal transcriptomes were compared by RNA-seq.

Results

RYGB resulted in 20-30% weight loss, normalized glycaemia and albuminuria and reduced indices of glomerular injury, specifically podocyte injury (foot process effacement). RYGB equivalent outcomes were obtained on all parameters following MB. A number of RYGB-discrete changes appear to relate to procedure rather than correction of disease. MB recapitulates many of the gene expression alterations observed after RYGB, but modifies expression of a much larger number of genes. A discrete and potentially beneficial response to RYGB was the induction of ALOX15 expression, a potential source of anti-inflammatory lipids.

Conclusion

Equivalent improvements in DKD are obtained following RYGB and matched MB. Shared transcriptional change may underpin comparable ultrastructural improvements, but similarities therein understate the degree of diversity at the molecular level. ALOX15 upregulation may be a useful component of RYGB amenable to targeting in non-surgical bariatric mimetic approaches.

Funding

  • Government Support - Non-U.S.