Cardiac energy metabolism disorder mediated by energy substrate imbalance and mitochondrial damage upon tebuconazole exposure

Tebuconazole exposure has been described as an increasing hazard to human health. An increasing number of recent studies have shown a positive association between tebuconazole exposure and cardiovascular disease risk, which is characterized by the reduction of adenosine triphosphate (ATP) synthesis. However, researches on the damage of tebuconazole exposure to energy metabolism and the related molecular mechanisms are limited. In the present study, male C57BL/6 mice were treated with tebuconazole at different low concentrations for 4 weeks. The results indicated that tebuconazole could accumulate in the heart and further induce the decrease of ATP content in the mouse heart. Importantly, tebuconazole induced an obvious shift in substrate utilization of fatty acid and glucose by disrupting their corresponding transporters (GLUT1, GLUT4, CD36, FABP3 and FATP1) expression, and significantly repressed the expression of mitochondrial biogenesis (Gabpa and Tfam) and oxidative phosphorylation (CS, Ndufa4, Sdhb, Cox5a and Atp5b) related genes in a dose-dependent manner. Further investigation revealed that these alterations were related to the IRS1/AKT and PPARγ/RXRα pathways. These findings contribute to a better understanding of triazole fungicide-induced cardiovascular disease by revealing the key indicators associated with this phenomenon.