Sleeve Gastrectomy Ameliorates Diabetes-Induced Cardiac Hypertrophy Correlates With the MAPK Signaling Pathway.

Qian Xu,Songhan Li,Huanxin Ding,Linchuan Li,Bowen Shi,Mingwei Zhong,Shuohui Dong,Guangyong Zhang

doi:10.3389/fphys.2021.785799

Abstract

Background: Cardiac hypertrophy as a main pathological manifestation of diabetic cardiomyopathy (DCM), is a significant complication of diabetes. Bariatric surgery has been proven to relieve DCM; however, whether it can alleviate diabetes-induced cardiac hypertrophy is undefined.Methods: Diabetic and obese rats were performed sleeve gastrectomy (SG) after having diabetes for 16weeks. The rats were euthanized 8weeks after SG. Metabolic parameters, heart function parameters, myocardial glucose uptake, morphometric and histological changes, and the expression level of mitogen-activated protein kinases (MAPKs) were determined and compared among the control group (CON group), diabetes mellitus group (DM group), sham operation group (SHAM group), and SG group.Results: Compared with the SHAM group, the blood glucose, body weight, insulin resistance, and other metabolic parameters were significantly improved in the SG group. There was also a marked improvement in myocardial morphometric and histological parameters after SG. Furthermore, the myocardial glucose uptake and heart function were reversed after SG. Additionally, the phosphorylation of MAPKs was inhibited after SG, including p38 MAPKs, c-Jun N-terminal kinases (JNKs), and extracellular signal-regulated kinases 1/2 (ERK1/2). The expression of DUSP6, which dephosphorylates ERK1/2, was upregulated after SG. These findings suggest that SG ameliorated diabetes-induced cardiac hypertrophy correlates with the MAPK signaling pathway.Conclusion: These results showed that diabetes-induced cardiac hypertrophy was ameliorated after SG was closely related to the inhibition of the MAPK signaling pathway and upregulation of DUSP6. Therefore, this study provides a novel strategy for treating diabetes-induced cardiac hypertrophy.

Highlights

During the past three decades, the number of people with diabetes mellitus has increased fourfold (Gibb and Hill, 2018)
In addition to the change in fasting blood glucose (FBG) and the serum insulin level, we found that the insulin resistance of the sleeve gastrectomy (SG) group was significantly improved compared with that of the SHAM group as assessed by homeostasis model assessment of insulin resistance (HOMA-IR) (Figures 2C–E)
SG significantly elevated the ratio of ejection fraction and fractional shortening, by approximately 20 and 10%, respectively (Figures 4D,E). All these results suggest that SG improved the degree of myocardial fibrosis and diabetes-induced cardiac hypertrophy, and it had a positive effect on the heart function impaired by DM

Summary

Introduction

During the past three decades, the number of people with diabetes mellitus has increased fourfold (Gibb and Hill, 2018). Cardiac hypertrophy and myocardial fibrosis are the main pathological features of DCM, with a significant association with death in DCM patients (Kobayashi and Liang, 2015; Jia et al, 2018). Bariatric surgery was only used to treat morbid obesity, but we have found that it has some benefits for the treatment of type 2 diabetes mellitus (T2DM) and its complications (Affinati et al, 2019; Ruze et al, 2020). Huang et al have shown that the bariatric surgery improved DCM and diabetes-induced cardiac hypertrophy clearly (Huang et al, 2018), yet the specific mechanism is unclear. Cardiac hypertrophy as a main pathological manifestation of diabetic cardiomyopathy (DCM), is a significant complication of diabetes. Bariatric surgery has been proven to relieve DCM; whether it can alleviate diabetes-induced cardiac hypertrophy is undefined

Methods

Results

Conclusion