Empagliflozin Restores Cardiac Metabolic Flexibility in Diet-induced Obese C57BL6/J Mice
Abstract
Abstract BackgroundSodium-glucose co-transporter type 2 (SGLT2) inhibitor therapy to treat type 2 diabetes unexpectedly reduced all-cause mortality and hospitalization due to heart failure in several large-scale clinical trials, and has since been shown to produce similar cardiovascular disease-protective effects in patients without diabetes. How SGLT2 inhibitor therapy improves cardiovascular disease outcomes remains incompletely understood. Metabolic flexibility refers to the ability of a cell or organ to adjust its use of metabolic substrates, such as glucose or fatty acids, in response to physiological or pathophysiological conditions, and is a feature of a healthy heart that may be lost during diabetic cardiomyopathy and in the failing heart. While several studies have addressed metabolic changes in hearts in response to SGLT2 inhibitor therapy, none have specifically assessed metabolic flexibility in an in vivo system. We therefore undertook the described studies to determine the effects of SGLT2 inhibitor therapy on cardiac metabolic flexibility in vivo in obese, insulin resistant mice.MethodsDiet-induced obese mice were treated with the SGLT2 inhibitor empagliflozin (EMPA; 10 mg/kg/d) for four weeks prior to study and compared with untreated obese and lean controls. We assessed changes in body weight and composition, plasma metabolites in response to fasting/re-feeding, cardiac hypertrophy by echocardiography, the response to ischemic stress following coronary artery…
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