Role of bariatric surgery in improving diabetic cardiomyopathy: Molecular mechanisms and therapeutic perspectives (Review)

Abstract

Diabetic cardiomyopathy (DCM), a significant complication of diabetes mellitus, is marked by myocardial structural and functional alterations due to chronic hyperglycemia. Despite its clinical significance, optimal treatment strategies are still elusive. Bariatric surgery via sleeve gastrectomy and Roux-en-Y gastric bypass have shown promise in treating morbid obesity and associated metabolic disorders including improvements in diabetes mellitus and DCM. The present study reviews the molecular mechanisms by which bariatric surgery improves DCM, offering insights into potential therapeutic targets. Future research should further investigate the mechanistic links between bariatric surgery and DCM, to evaluate the benefits and limitations of these surgical interventions for DCM treatment. The present study aims to provide a foundation for more effective DCM therapies, contributing to the advancement of patient care.

Keywords: bariatric surgery; diabetic cardiomyopathy; endoplasmic reticulum stress; mechanism; myocardial glucose uptake.

Figure 1.

Possible mechanisms by which bariatric surgery improves DCM. Bariatric surgery may improve DCM by maintaining calcium homeostasis, regulating the gut-heart axis, reducing myocardial fatty acid formation, reducing myocardial mitochondrial autophagy, improving myocardial glucose uptake, inhibiting inflammasome activation and reducing endoplasmic reticulum stress. DCM, diabetic cardiomyopathy; RYGB, Roux-en-Y gastric bypass; SG, sleeve gastrectomy.

Figure 2.

Possible mechanisms of DJB and SG in improving DCM. DJB promotes GLUT-4 translocation and restores MGU by activating the PI3K/AKT signaling pathway and downstream substrates. SG improves diabetes-induced myocardial hypertrophy by inhibiting the MAPK signaling pathway. DJB, duodenal-jejunal bypass; SG, sleeve gastrectomy; DCM, diabetic cardiomyopathy; GLUT-4, glucose transporter 4; PI3K, phosphatidylinositol 3-kinase; Akt, protein kinase B; MGU, myocardial glucose uptake; P, phosphorylated; JNK, c-Jun N-terminal kinase; ERK1/2, extracellular signal-regulated kinase 1/2; TBC1D1, TBC1 domain family member 1.

Figure 3.

Possible mechanisms by which bariatric surgery improves ER stress in cardiomyocytes. SG and DJB improve ER stress in cardiomyocytes by decreasing signaling molecules related to apoptosis and ER stress in cardiomyocytes such as GRP78, PERK, P-PERK, CHOP and caspase 12. DJB, duodenal-jejunal bypass; SG, sleeve gastrectomy; PERK, protein kinase R-like endoplasmic reticulum kinase; CHOP, C/EBP homologous protein, ER endoplasmic reticulum; P, phosphorylated.

Figure 4.

Schematic representation of the formation of autophagy inhibition/activation. Obesity or diabetic cardiomyopathy leads to over inhibition/activation of myocardial autophagy, which can be ameliorated by bariatric surgery. SG, sleeve gastrectomy; DJB, duodenal-jejunal bypass; RYGB, Roux-en-Y gastric bypass; ROS, reactive oxygen species; DCM, diabetic cardiomyopathy; GLP-1, glucagon-like peptide-1.