An attempt to reverse cardiac lipotoxicity by aerobic interval training in a high-fat diet- and streptozotocin-induced type 2 diabetes rat model

Abstract

Background Diabetes mellitus (DM) is an important risk factor for cardiovascular disease. Aerobic interval training (AIT) has been recommended to patients as a non-pharmacological strategy to manage DM. However, little is known about whether AIT intervention at the onset of DM will reverse the process of diabetic cardiomyopathy (DCM). In this study, we sought to evaluate whether AIT can reverse the process of DCM and explore the underlying mechanisms. Methods Fifty Wistar rats were randomly divided into a control group (CON), DCM group (DCM) and AIT intervention group (AIT). A high-fat diet and streptozotocin (STZ) were used to induce diabetes in rats in the DCM group and AIT group. Rats in the AIT group were subjected to an 8-week AIT intervention. Fasting blood glucose (FBG), lipid profiles and insulin levels were measured. Haematoxylin and eosin (HE) staining and oil red O staining were used to identify cardiac morphology and lipid accumulation, respectively. Serum BNP levels and cardiac BNP mRNA expression were measured to ensure the safety of the AIT intervention. Free fatty acid (FFA) and diacylglycerol (DAG) concentrations were analysed by enzymatic methods. AMPK, p-AMPK, FOXO1, CD36 and PPARα gene and protein expression were detected by RT-PCR and Western blotting. Results AIT intervention significantly reduced rat serum cardiovascular disease risk factors in DCM rats (P < 0.05). The safety of AIT intervention was illustrated by reduced serum BNP levels and cardiac BNP mRNA expression (P < 0.05) after AIT intervention in DCM rats histological analysis and FFA and DAG concentrations revealed that AIT intervention reduced the accumulation of lipid droplets within cardiomyocytes and alleviated cardiac lipotoxicity (P < 0.05). CD36 and PPARα gene and protein expression were elevated in the DCM group, and these increases were reduced by AIT intervention (P < 0.01). The normalized myocardial lipotoxicity was due to increased expression of phosphorylated AMPK and reduced FOXO1 expression after AIT intervention. Conclusion AIT intervention may alleviate cardiac lipotoxicity and reverse the process of DCM through activation of the AMPK–FOXO1 pathway.

Cadmium exposure induces cardiac glucometabolic dysregulation and lipid accumulation independent of pyruvate dehydrogenase activity

“…In correlation with earlier observation, an increase in FFAs was also observed in obese rats [ 61 ]. Histology and cardiac tissue findings have also shown that within cardiomyocytes, DCM hearts mount up lipid drops, followed by elevated levels of FFA [ 62 ]. Induced by a mismatch between fatty acid uptake and oxidation, the accumulation of triglycerides in the heart develops as a determinant of cardiac damage, primarily through accumulation of free radicals and successive activation of apoptosis [ 63 ].…”

Cardiac-selective gene delivery of medium-chain acyl-CoA dehydrogenase (MCAD) does not protect against diabetes-induced cardiac dysfunction

“…Our nding of reduced PLIN5 levels in hearts with greater FLAG-MCAD expression suggest that rAAV6:MCAD treatment can reduce overall lipid accumulation in the diabetic heart, although the effect was mild and was not su cient to improve diastolic function. An 8-week exercise training program initiated 2 weeks after the induction of diabetes in rats prevented cardiac lipid accumulation, and this was associated with preserved diastolic and systolic function [70]. Thus, therapeutic strategies that have a more profound effect on reducing cardiac steatosis are likely to be more successful than rAAV6:MCAD gene therapy at improving outcomes in settings of diabetes.…”

Misuse of Cardiac Lipid upon Exposure to Toxic Trace Elements—A Focused Review

“…The heart function highly depends on the capacity of the metabolism. Cd increased the weight of the heart in a rat model [ 47 ]. Similarly, another study showed that toxic chemicals increase organ weight due to the accumulation of lipids and inflammation [ 14 ].…”

“…During diabetic cardiomyopathy, there is an elevated FFA level which contributes to lipid accumulation in the heart. Also, the unbalance between the fatty acid uptake and its oxidation leads to TG accumulation, such as cardiac lipotoxicity, and decreases ATP in the heart, potentially leading to cardiac damage [ 47 ].…”