Background: Asprosin is a novel fasting glucogenic adipokine discovered in 2016. Asprosin induces rapid glucose releases from the liver. However, its molecular mechanisms and function are still unclear. Adaptation of energy substrates from fatty acid to glucose is recently considered a novel therapeutic target in heart failure treatment. We hypothesized that the asprosin is able to modulate cardiac mitochondrial functions and has important prognostic implications in dilated cardiomyopathy (DCM) patients.
Methods: We prospectively enrolled 50 patients (86% male, mean age 55 ± 13 years) with DCM and followed their 5-year major adverse cardiovascular events from 2012 to 2017. Comparing with healthy individuals, DCM patients had higher asprosin levels (191.2 versus 79.7 ng/mL, P < 0.01).
Results: During the 5-year follow-up in the study cohort, 16 (32.0%) patients experienced adverse cardiovascular events. Patients with lower asprosin levels (< 210 ng/mL) were associated with increased risks of adverse clinical outcomes with a hazard ratio of 7.94 (95% CI 1.88-33.50, P = 0.005) when compared patients with higher asprosin levels (≥ 210 ng/mL). Using cardiomyoblasts as a cellular model, we showed that asprosin prevented hypoxia-induced cell death and enhanced mitochondrial respiration and proton leak under hypoxia.
Conclusions: In patients with DCM, elevated plasma asprosin levels are associated with less adverse cardiovascular events in five years. The underlying protective mechanisms of asprosin may be linked to its functions relating to enhanced mitochondrial respiration under hypoxia.
Keywords: Asprosin; Dilated cardiomyopathy; Heart failure; Hypoxia; Obesity.