Abstract
ObjectiveThe aim of this study was to explore the protective effects and the regulatory mechanisms of bariatric surgery on kidney injury in diabetic rats.MethodsWe established a useful type 2 diabetic rat model using high-fat and high-sugar diet feeding following low-dose streptozotocin (STZ) treatment. Sprague–Dawley (SD) rats were randomly divided into the following groups: control (Con) group, diabetic nephropathy (DN) group, and duodenal–jejunal bypass (DJB) surgery group. The food intake and body weight of rats were monitored and the glucose tolerance test (OGTT) test was performed every 2 weeks. The glomerular filtration rate (GFR) and urinary albumin excretion rate (UAFR) were measured to assess renal function. Hematoxylin–eosin (H&E), periodic acid–Schiff (PAS), and Masson staining were used to evaluate renal histopathological changes. TUNEL assay was performed to detect cell apoptosis. The expressions of oxidative stress factors and inflammatory factors in the renal tissues of rats were detected by ELISA. The expressions of PPARα, reactive oxygen species (ROS), and NF-κB were detected by immunofluorescence. For in vitro experiment, HK2 cells cultured with high glucose were treated with PPARα agonist, PPARα antagonist, and adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) agonist. The expressions of AMPK/PPARα/NF-κB signaling pathway-related proteins were detected by Western blot.ResultsBariatric surgery improved the glucose tolerance of DN rats. The GFR was decreased, the promotion of urinary albumin excretion rate (UAER) was inhibited, and the renal injury was alleviated. The extracellular matrix fraction was decreased and the renal function was improved. Meanwhile, bariatric surgery activates PPARα, inhibits ROS release, reduces oxidative stress injury, and reduces renal cell apoptosis. In vitro experiment results showed that the AMPK activator could activate PPARα, downregulate NF-κB, and inhibit inflammatory response. The phosphorylation of AMPK was inhibited by PPARα antagonism.ConclusionBariatric surgery can activate PPARα, inhibit oxidative stress injury, and improve glucose metabolism and renal function in DN rats.
Highlights
Diabetes mellitus (DM) has become a significant chronic disease that endangers people’s lives and health
In vitro experiment results showed that the AMPK activator could activate PPARα, Bariatric Surgery on PPARα downregulate NF-κB, and inhibit inflammatory response
It was reported that the disorder of glucose metabolism caused by T2DM can promote oxidative stress responses and induce the apoptosis of renal tubular epithelial cells, which are the main pathological mechanisms leading to diabetic nephropathy (DN) (Calabrese et al, 2007; Rani et al, 2016)
Summary
Diabetes mellitus (DM) has become a significant chronic disease that endangers people’s lives and health. Its clinical types include type I diabetes (T1DM), type II diabetes (T2DM), and gestational diabetes mellitus (GDM) (Guay and Regazzi, 2013). Diabetic nephropathy (DN) is the most common microvascular complication in patients with T2DM (Vanaclocha-Espi et al, 2019). It was reported that the disorder of glucose metabolism caused by T2DM can promote oxidative stress responses and induce the apoptosis of renal tubular epithelial cells, which are the main pathological mechanisms leading to DN (Calabrese et al, 2007; Rani et al, 2016). Studies have proven that bariatric surgery can effectively downregulate the disorder of glucose metabolism and lipid metabolism in the high-glucose environment caused by T2DM and inhibit the accumulation of oxidative stress products (Lone et al, 2020). Whether bariatric surgery could improve the type II diabetes accompanying complications through regulating glycemia is still not clarified
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
