α-ALA Attenuates Cardiac Injury in Diabetic Heart Disease Mice by Modulating Inflammation and AMPKα1.

Abstract

Introduction: Diabetic heart disease (DHD) is systolic and/or diastolic dysfunction of the heart muscle that occurs in patients with the presence of Type 2 diabetes mellitus. AMPKα1, a key regulator of glucose metabolism, has been shown to promote glucose uptake and catabolism. Alpha-linolenic acid (α-ALA) is an essential fatty acid that helps to prevent cardiovascular disease and is very important for human health. However, its role as a medical agent in preventing DHD by modulating AMPKα1is unknown.

Methods: An experimental type 2 diabetic mouse model was established by treating animals with a high-fat diet (HFD) for four weeks and intraperitoneal injection of streptozotocin (STZ) (50 mg/kg body weight). After induction of type 2 diabetes, the animals were treated orally with α-ALA (2 or 4 g/kg) for twelve weeks.

Results: The type 2 diabetic mice showed an increase in blood glucose levels, a decrease in body weight and cardiac dysfunction. Diabetic mice treated with α-ALA attenuated hyperglycaemia, dyslipidaemia, and cardiac dysfunction. In addition, α-ALA improved histological changes and fibrosis in HFD/STZ-induced mice. Type 2 diabetes in mice exacerbated the inflammatory status. α-ALA treatment significantly attenuated inflammation in diabetic hearts. The underlying mechanisms for this attenuation involved modulation of AMPKα1.

Conclusion: The results of this study provide evidence that α-ALA protects against HFD/STZ (T2DM)-induced cardiac injury by alleviating inflammation and upregulating AMPKα1.