# Duodenal‐jejunal bypass surgery activates eNOS and enhances antioxidant system by activating AMPK pathway to improve heart oxidative stress in diabetic cardiomyopathy rats

## TL;DR

Duodenal-jejunal bypass surgery improves heart oxidative stress in diabetic rats by activating the AMPK pathway, which enhances the antioxidant system and eNOS activity.

## Contribution

The study reveals that DJB surgery improves heart oxidative stress in diabetic rats via the AMPK pathway, not just by lowering blood glucose.

## Key findings

- DJB activates the AMPK pathway, increasing eNOS phosphorylation and antioxidant system activity in diabetic rats.
- AMPK activation by DJB reduces oxidative stress in heart tissue and H9C2 cells.
- Improvement is not solely due to blood glucose reduction but involves AMPK-mediated mechanisms.

## Abstract

Diabetic cardiomyopathy is a serious complication of obesity with type 2 diabetes and is a major cause of mortality. Metabolic surgery, such as duodenal‐jejunal bypass (DJB), can effectively improve diabetic cardiomyopathy; however, the underlying mechanisms remain elusive. Oxidative stress is one of the pivotal mechanisms of diabetic cardiomyopathy. Our objective was to investigate the effect and potential mechanisms of DJB on oxidative stress in the heart of diabetic cardiomyopathy rats.

High‐fat diet combined with intraperitoneal injection of streptozotocin was used to establish diabetic cardiomyopathy rats. DJB was performed on diabetic cardiomyopathy rats, and high glucose and palmitate were used to simulate diabetic cardiomyopathy in H9C2 cells in vitro. Sera from different groups of rats were used for experiments in vivo and in vitro.

DJB effectively improved oxidative stress and activated the adenosine monophosphate (AMP)‐activated protein kinase (AMPK) pathway to increase endothelial nitric oxide synthase (eNOS) phosphorylation level and the expression of antioxidative system‐related proteins and genes in the heart of diabetic cardiomyopathy rats. AMPK agonists and serum from DJB rats activated the AMPK pathway to increase eNOS phosphorylation level and the expression of antioxidative system‐related proteins and genes and decreased the content of reactive oxygen species in H9C2 cells, but this improvement was almost eliminated by the addition of AMPK inhibitors.

DJB activates eNOS and enhances the antioxidant system by activating the AMPK pathway—and not solely by improving blood glucose—to improve oxidative stress in the heart of diabetic cardiomyopathy rats.

Highlights

This study revealed that duodenal‐jejunal bypass (DJB) attenuated oxidative stress in diabetic cardiomyopathy rats by activating the adenosine monophosphate (AMP)‐activated protein kinase (AMPK) pathway, thereby augmenting the antioxidative system and elevating the phosphorylation level of nitric oxide synthase (eNOS).The application of sera obtained from distinct groups and the agonist of AMPK pathway to stimulate H9C2 cells revealed that DJB intervention partially alleviated heart oxidative stress by activating the AMPK pathway, rather than solely by improving blood glucose levels.

This study revealed that duodenal‐jejunal bypass (DJB) attenuated oxidative stress in diabetic cardiomyopathy rats by activating the adenosine monophosphate (AMP)‐activated protein kinase (AMPK) pathway, thereby augmenting the antioxidative system and elevating the phosphorylation level of nitric oxide synthase (eNOS).

The application of sera obtained from distinct groups and the agonist of AMPK pathway to stimulate H9C2 cells revealed that DJB intervention partially alleviated heart oxidative stress by activating the AMPK pathway, rather than solely by improving blood glucose levels.