Irisin is a novel muscle-secreted hormone (myokine) that is produced through the cleavage of a transmembrane protein, fibronectin type III domain-containing protein 5 (FNDC-5) [1]. Although the exact details of FNDC-5 cleavage are not completely understood, a disintegrin and metalloproteinase (ADAM) family member, ADAM-10 has been proposed as a candidate protease that cleaves FNDC-5 [2]. A previous study demonstrated that angiotensin II upregulates ADAM-10, indicating the involvement of the renin-angiotensin system in irisin production [2]. FNDC-5 is mainly expressed in muscle tissues, including skeletal and cardiac muscles, making muscle the primary source of irisin production [3, 4]. Notably, other tissues, such as liver, thyroid, adrenal grand, white adipose tissue, and central nervous system, also express FNDC-5 and can produce irisin [1]. Originally, irisin was identified as a mediator of exercise-induced metabolic improvements, attributable to an increase in energy expenditure due to the browning of white adipose tissue [3]. However, an increasing number of studies have explored the physiological and pathophysiological roles of irisin in the regulation of blood pressure (BP) and hypertension.
Animal studies found that irisin administration led to a significant reduction in BP in both Zucker diabetic fatty rats and spontaneously hypertensive rats, accompanied by improvements in renal sodium retention, arterial endothelial dysfunction, and oxidative stress within the paraventricular nucleus [5,6,7]. In humans, it seems to have been established that circulating irisin levels in patients with chronic kidney disease are significantly decreased compared to those in healthy controls [8, 9]. Conversely, clinical studies have reported conflicting results regarding the association between circulating irisin levels and BP in patients with chronic kidney disease [10,11,12,13].
The present study by Wang et al. [14] evaluated the clinical associations between serum irisin levels and BP in 350 patients undergoing dialysis at the Xuanwu Hospital Capital Medical University. This study included patients aged >18 years who were undergoing dialysis for >3 months and agreed to participate. Patients with cancer, overt infection, or significant clinical events within 3 months before study enrollment were excluded. In total, 300 patients were found to be eligible for inclusion in the study and were thus enrolled. The average BP was determined based on the morning and evening BP levels checked at home for 7 consecutive days to exclude the effects of BP variability in the peri-dialysis period. The participants were categorized into hypertensive (systolic BP ≥ 135 mmHg and/or diastolic BP ≥ 85 mmHg) and normotensive (systolic BP < 135 mmHg and diastolic BP < 85 mmHg) groups based on the home BP levels, regardless of the use of anti-hypertensive agents. Compared to the normotensive group, the hypertensive group had significantly lower serum irisin levels. Pearson correlation analysis revealed that serum irisin levels were negatively correlated with systolic BP. Furthermore, multivariate analysis demonstrated that lower serum irisin levels were independently associated with higher BP levels after adjustment for confounders.
Few clinical studies have provided evidence regarding the association between circulating irisin levels and BP. The present study by Wang et al. provides new insights into this association among patients undergoing hemodialysis. However, given the cross-sectional design of the study [10,11,12,13], the causal relationship between circulating irisin levels and BP remains unclear. In addition, given the conflicting results of previous clinical studies, it is possible that the clinical significance of circulating irisin levels varies among disease types. Therefore, further evidence is needed to clarify these uncertainties, which would enhance our understanding of the mechanisms underlying hypertension and facilitate the development of novel anti-hypertensive agents.
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Azushima, K., Tamura, K. Association between serum irisin levels and blood pressure in patients undergoing hemodialysis. Hypertens Res 47, 548–550 (2024). https://doi.org/10.1038/s41440-023-01508-3
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DOI: https://doi.org/10.1038/s41440-023-01508-3