The Novel Mechanism of Asprosin in Congestive Heart Failure

Exercise, adipose tissues, and cardiovascular diseases have close interactions. The machinery among exercise, adipose tissues, and cardiovascular diseases involves multiple different factors, such as environmental cues, genetic expressions, behavioral changes, and nutrients homeostasis. Our laboratory has been studying the exercise-related adipokines for several years. Asprosin is a novel fasting glucogenic adipokine discovered in 2016. Asprosin induces rapid glucose release from the liver through stimulating the G-protein-cAMP-PKA axis. By inhibiting anorexigenic proopiomelanocortin-positive neurons in a GABA-dependent manner, asprosin stimulates appetite and physiological drive to accumulate adiposity and increase body weight. The role of asprosin in hearts is still unknown. Cardiac energy expenditure and mitochondrial homeostasis are critical in the pathogenesis of heart failure. Adaptation of substrates from fatty acid to glucose is recently considered a novel therapeutic target in heart failure treatment. Our preliminary data have shown that adipokine-asprosin is able to modulate cardiac energy metabolism through mitochondria and has important prognostic implications in dilated cardiomyopathy patients. Data from our group showed that the patients with dilated cardiomyopathy had higher asprosin levels (191.2 versus 79.7 ng/mL, p＜0.01). During the 5-year follow-up in the study cohort, 18 (36.0%) patients experienced an adverse cardiovascular event. Patients with lower asprosin levels (＜210 ng/mL) were associated with increased risks of adverse clinical outcomes with a hazard ratio of 1.48 (95% CI 1.31-2.22; P＜0.001) when compared with higher asprosin levels (≥210 ng/mL). Based on our preliminary data, asprosin may have important roles in the cardiovascular system. Therefore, we have proposed three specific aims to investigate the role of asprosin in the heart and its relationships with cardiomyocytes.Our first aim is to study the roles of asprosin in apoptosis, hypoxia, autophagy, and mitochondria. We will study the molecular mechanisms of asprosin and its protective signatures in autophagy and mitochondria in the second aim. Because decreases in asprosin result in worsening cardiovascular outcomes in humans, we will determine whether the administration of asprosin can protect mice from congestive heart failure. We will investigate the asprosin receptor function in the third aim and study its role in heart failure. We believe that complete these 3 aims can provide novel aspects of heart failure treatment and links between obesity, adipose tissue, and heart failure.

Project ID:PC10907-0897
External Project ID:MOST109-2314-B182-070-MY3