Endocrine Abstracts

Background: Asprosin is a novel adipokine involved in appetite and glucose regulation. During obesity, circulating asprosin is increased, which leads to increased inflammation and can disrupt cellular functions such as mitochondrial respiration. Asthma is a comorbidity of obesity, with both diseases sharing an inflammatory profile and mitochondrial dysfunction. This study investigated the molecular links between asthma and obesity, by exploring whether asprosin causes mitochondrial dysfunction in airway epithelial cells, as experienced in asthma.

Methods: Human airway epithelial cells (BEAS2B-R1) were treated with 10 ng/mL asprosin for 6 and 24hrs. Mitochondrial function analysis was undertaken using the mitochondrial stress test assay on the Seahorse XFe Analyzer to measure oxygen consumption rate (OCR). Mitochondrial copy number was assessed using RT-qPCR, using taqman gene expression assays for BECN1 and mtND1. Cells were stained for total and active mitochondria using MitoTracker dye.

Results: Asprosin treatment initially reduced the mitochondrial copy number by 57% at 6hr compared to control (P<0.05), however at 24hr asprosin treated cells had 10% more mitochondria than control (P<0.05). The ratio of active to inactive mitochondria was unchanged with asprosin treatment at 6hr, but was decreased by 51% at 24hr (P<0.0001), suggesting that the increase in mitochondrial copy number is compensating for this inactivity. This is highlighted by the mitochondrial stress test which showed no difference in OCR between control and asprosin treated cells at 6 or 24hrs.

Conclusion: Asprosin impacts the total number of mitochondria, and the number of active mitochondria in airway epithelial cells, forcing mitochondria to work harder to achieve the same OCR. This could be an early indicator of mitochondrial dysfunction which is present in asthma. As such, it is possible that asprosin may drive the link between obesity and asthma, making it a possible target to reduce such disease.