Heart failure is a prevalent disease worldwide. While it is well accepted that heart failure involves changes in myocardial energetics, what alterations that occur in fatty acid oxidation and glucose oxidation in the failing heart remains controversial. The goal of the study are to define the energy metabolic profile in heart failure induced by obesity and hypertension in aged female mice, and to attempt to lessen the severity of heart failure by stimulating myocardial glucose oxidation. 13-Month-old C57BL/6 female mice were subjected to 10 weeks of a 60% high-fat diet (HFD) with 0.5 g/L of Nω-nitro-l-arginine methyl ester (L-NAME) administered via drinking water to induce obesity and hypertension. Isolated working hearts were perfused with radiolabeled energy substrates to directly measure rates of myocardial glucose oxidation and fatty acid oxidation. Additionally, a series of mice subjected to the obesity and hypertension protocol were treated with a pyruvate dehydrogenase kinase inhibitor (PDKi) to stimulate cardiac glucose oxidation. Aged female mice subjected to the obesity and hypertension protocol had increased body weight, glucose intolerance, elevated blood pressure, cardiac hypertrophy, systolic dysfunction, and decreased survival. While fatty acid oxidation rates were not altered in the failing hearts, insulin-stimulated glucose oxidation rates were markedly impaired. PDKi treatment increased cardiac glucose oxidation in heart failure mice, which was accompanied with improved systolic function and decreased cardiac hypertrophy. The primary energy metabolic change in heart failure induced by obesity and hypertension in aged female mice is a dramatic decrease in glucose oxidation. Stimulating glucose oxidation can lessen the severity of heart failure and exert overall functional benefits.

心力衰竭是世界范围内的一种流行疾病。虽然人们普遍认为心力衰竭涉及心肌能量学的变化，但衰竭心脏中脂肪酸氧化和葡萄糖氧化发生的变化仍然存在争议。该研究的目的是确定老年雌性小鼠肥胖和高血压引起的心力衰竭的能量代谢特征，并尝试通过刺激心肌葡萄糖氧化来减轻心力衰竭的严重程度。 13 个月大的 C57BL/6 雌性小鼠接受 10 周的 60% 高脂饮食 (HFD)，并通过饮用水给予0.5 g/L Nω-硝基-l-精氨酸甲酯 ( L -NAME)从而诱发肥胖和高血压。用放射性标记的能量底物灌注离体的工作心脏，以直接测量心肌葡萄糖氧化和脂肪酸氧化的速率。此外，一系列接受肥胖和高血压方案的小鼠接受丙酮酸脱氢酶激酶抑制剂（PDKi）治疗，以刺激心脏葡萄糖氧化。接受肥胖和高血压方案的老年雌性小鼠体重增加、葡萄糖耐受不良、血压升高、心脏肥大、收缩功能障碍和存活率降低。虽然衰竭心脏中的脂肪酸氧化率没有改变，但胰岛素刺激的葡萄糖氧化率明显受损。 PDKi 治疗可增加心力衰竭小鼠的心脏葡萄糖氧化，同时改善收缩功能并减少心脏肥厚。老年雌性小鼠肥胖和高血压引起的心力衰竭的主要能量代谢变化是葡萄糖氧化的急剧减少。刺激葡萄糖氧化可以减轻心力衰竭的严重程度并发挥整体功能益处。