Roux-en-Y Esophagojejunostomy Ameliorates Renal Function Through Reduction of Renal Inflammatory and Fibrotic Markers in Diabetic Nephropathy.

BACKGROUND

Roux-en-Y bariatric surgery has been shown to have a remarkable and sustainable improvement in type 2 diabetes. Recent clinical studies have shown that bariatric surgery can improve or halt the development of diabetic microvascular complications such as nephropathy. However, the exact underlying mechanisms of surgical procedures are unknown. Here, we have investigated the effects of Roux-en-Y esophagojejunostomy (RYEJ) on renal function and inflammation and fibrosis biomarkers for renal injury in type 2 diabetic rats.

METHODS

Sprague-Dawley rats with high fat diet and streptozotocin (STZ)-induced diabetes were randomly assigned into four groups: diabetic nephropathy (DN), DN treated with food restriction (DN-FR), DN treated with RYEJ surgery (DN-RYEJ), and DN-RYEJ sham (n = 6/group). Age-matched normal rats were assigned as control group. RYEJ and sham surgeries were performed. Hyperinsulinemic-euglycemic clamps with tracer infusion were completed to assess insulin sensitivity. Twenty-four hour urine albumin excretion rate (UAER) and glomerular filtration rate (GFR) were measured. The renal pathological injury was assessed by hematoxylin and eosin (HE) staining. Kidney messenger RNA (mRNA) and/or protein content/distribution of phospho-c-Jun NH2-terminal kinase (JNK), monocyte chemoattractant protein (MCP)-1, transforming growth factor (TGF)-β1, and mitogen-activated protein kinase phosphatase 5 (MKP5) were evaluated by real-time PCR and/or Western blotting/immunohistochemistry.

RESULTS

Roux-en-Y esophagojejunostomy improved insulin sensitivity. RYEJ ameliorated renal function by improving UAER and GFR and attenuated glomerular hypertrophy after surgery. RYEJ also significantly downregulated the levels of JNK-mediated inflammatory response and upregulated the level of the anti-inflammatory mediator MKP5.

CONCLUSION

Roux-en-Y esophagojejunostomy alleviates insulin resistance. RYEJ surgery ameliorated renal function and attenuated glomerular hypertrophy in a DN rat model. The considerable nephroprotective function may be mainly attributed to the reduced inflammatory and fibrotic biomarkers after RYEJ. The improvements in renal function and inflammation are not wholly dependent on the magnitude of weight loss.