Overconsumption of fructose has been linked to the development of systemic metabolic and cardiac diseases, yet few studies have focused on the link between cardiac fructose metabolism and the development of heart disease. Low-oxygen complex exercise is considered an effective means of treating and preventing metabolic diseases and improving cardiac function, however, it is unclear, the link between low-oxygen complex exercise and high-fructose-induced heart disease. Therefore, the aim of this study was to investigate the effect of hypoxic complex exercise on heart disease on a high fructose diet. The results of the study found that hypoxic compound exercise improved the upregulation of inflammatory factor Upd3 and systemic fat accumulation in the heart induced by high fructose diet by inhibiting the expression of KHK gene in the heart
and it improved the impaired cardiac rhythmic function and pumping function, improved the disorder of myofilament fiber arrangement, reduced the level of cardiac oxidative stress, and reduced cardiac collagen deposition. In addition, cardiac KHK-specific knockdown had the same effect on high fructose diet hearts. Compared with single KHK cardiac-specific knockdown or hypoxic combination exercise, hypoxic combination exercise combined with KHK cardiac-specific knockdown was superior in improving the high-fructose diet-induced increase in arrhythmia index, systolic and diastolic dysfunction, and decrease in fractional shortening. Therefore, we conclude that hypoxic complex exercise improved high-fructose diet-induced cardiac rhythmic function and pumping dysfunction by reducing KHK expression.