Sodium glucose co-transporter 2 inhibition prevents muscle energy metabolism changes in infarcted rats

Abstract

Introduction Skeletal muscle energy metabolism is commonly altered in heart failure patients, with a metabolic shift from oxidative to glycolytic muscle fiber. These changes contribute to reduced functional capacity. Sodium glucose co-transporter type 2 (SGLT2) inhibitors improve cardiovascular outcomes in both diabetic and non-diabetic patients, as well as those with and without heart failure. However, the effects of SGLT2 inhibitors on skeletal muscle during heart failure have not been established. The aim of this study was to assess the metabolic effect of empagliflozin (EMPA) on skeletal muscle of rats with myocardial infarction (MI)-induced heart failure. Methods One week after MI induction or simulated surgery, male Wistar rats were divided into four groups: Sham (n=10), Sham+Empa (n=12), MI (n=10), and MI+Empa (n=09). EMPA was added to rat chow (5 mg/kg/day). Rats were supplied with ad libitum water and chow for 12 weeks. Infarct size was measured by histological analysis. Metabolic enzyme activity in the soleus muscle was assessed by spectrophotometry. Statistical analysis: ANOVA and Tukey, and Student's t tests. Results Only rats with infarction size greater than 35% of total left ventricle area were included in this study. Infarction size did not differ between infarcted groups (MI 41.8±4.2; MI+Empa 40.7±5.7 of total left ventricle area). In the MI soleus muscle, metabolic enzyme activity of glucose-6-phosphate-dehydrogenase, citrate synthase and beta-hydroxy-acyl-dehydrogenase was higher than the Sham group. These changes were not observed in the MI+Empa group. MI+Empa had lower hexokinase, phosfructokinase, and pyruvate kinase activity (glycolytic metabolism enzymes), and lower citrate synthase and glucose-6-phosphate-dehydrogenase activity than MI. Conclusion Chronic treatment with SGLT2 inhibitor empagliflozin prevents metabolic abnormalities in skeletal muscle in infarcted rats. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): CAPES, CNPq, FAPESP