Background
In modern society, a chronic high-calorie diet and a sedentary lifestyle has resulted in obesity becoming a worldwide epidemic issue [
1]. Obesity-related cardiovascular risk factors (CVRFs), such as diabetes mellitus, hypertension and dyslipidemia, have promoted the development and progression of atherosclerosis, which contributes to the leading cause of death associated with cardiovascular diseases globally [
2,
3]. It has been noted that the clustering of CVRFs in an individual results in a higher risk of the development of cardiovascular diseases than in an individual that carries only a single CVRF [
2‐
4]. Correspondingly, it has been well recognized that reducing CVRFs prevents the occurrence of atherosclerosis and even cardiovascular diseases among the obese population [
5,
6] Thus, identification of available biomarkers that are related to CVRFs is imperative to predict and monitor the pathogenesis and progression of cardiovascular diseases.
Irisin is a new myokine that was initially found to be secreted into the blood stream by skeletal muscles during exercise. Irisin can stimulate the browning of white adipose tissue, to improve glucose metabolism and thus increase energy expenditure [
7]. More recent studies have shown that other tissues/organs, such as the heart, brain, tongue, rectum and adipose tissue also secret irisin [
8‐
10]. Clinical studies have shown a correlation between the circulating levels of irisin and cardiovascular diseases. For instance, subjects with coronary artery disease or calcification have lower serum irisin levels than in healthy subjects [
11‐
13], and a lower serum irisin concentration was found to be inversely associated with endothelial dysfunction [
14]
and cardiovascular complication among diabetic patients [
15]. Moreover, a meta analysis involving 7 case–control studies confirmed that irisin levels were significantly lower in patients with coronary artery disease [
16].
In addition, a number of studies conducted among Chinese subjects also showed a relationship between circulating irisin levels and CVRFs. For example, elevated serum irisin levels have been linked to the reduced metabolic syndrome and negatively associated with the dysregulated lipid profile [
17], while decreased serum irisin levels are associated with type 2 diabetes mellitus or insulin resistance [
18]. Hence, serum irisin levels may offer a value in predicting beneficial effects of exercise on metabolism, as well as the risk of the development of cardiovascular diseases, such as acute heart failure [
19].
Previous studies have mainly focused on the relationship between serum irisin levels and cardiovascular diseases as well as a single CVRF; the association between serum irisin levels and the clustering of CVRFs has not been well explored. Moreover, whether serum irisin levels could serve as a biomarker for cardiovascular diseases among a Chinese overweight/obese population is unclear. In the present study, we explored the association between serum irisin levels and a single CVRF, as well as the clustering of CVRFs, and interrogated the potential of serum irisin as a biomarker of cardiovascular diseases among a Chinese overweight/obese population.
Discussion
The major finding from the present study was that serum irisin levels were negatively associated with the clustering of the major CVRFs among the Chinese overweight/obese population. To the best of our knowledge, this is the first study to investigate the relationship between serum irisin levels and the clustering of CVRFs among the Chinese adult overweight/obese populations.
Irisin was initially identified as a skeletal muscle-secreted factor. However, numerous studies have demonstrated that irisin is implicated in mediating the function of several tissues/organs and has been proposed as a biomarker of different diseases, including metabolic disease, sarcopenia and endothelial dysfunction [
26‐
28]. In the cardiovascular field, previous studies that have investigated the adult population have mainly focused on the association of circulating irisin levels with a single CVRF, for example, with either diabetes mellitus or dyslipidemia. Serum irisin levels have been shown to be negatively associated with dyslipidemia, especially TC and LDL-C, among men [
29]. However, irisin levels were found to be positively associated with HDL-C among patients with chronic kidney disease [
30]. In the present study, we found that the risk for a single CVRF, such as smoking or dyslipidemia, was lower in the high irisin group than in the low irisin group, indicating an inverse correlation between serum irisin and smoking/dyslipidemia. Furthermore, we showed that there was a positive correlation between serum irisin and HDL-C, which is an acknowledged protective factor of cardiovascular disease. Notably, there was a negative association between serum irisin and smoking, offering another layer of evidence for a correlation between low serum irisin levels and cardiovascular diseases. Smoking may increase the circulating Interleukin-6 level which is a proinflammatory cytokine [
31]. Inflammation may decrease the expression of
FNDC5 and cause the low level of serum irisin. Previously, Yan et al
. revealed that the circulating irisin level was negatively associated with raised plasma glucose among the central obese population [
17]. Additionally, a meta-analysis involving 17 cross-sectional and 6 case control studies also suggested that diabetes mellitus patients had lower circulating irisin levels than those of controls [
18]. In the present study, we also found an inverse correlation between the serum irisin level and FPG and the prevalence of diabetes mellitus among the overweight/obese populations. However, this correlation disappeared after adjustment for gender, physical activity and other CVRFs. Thus, the exact correlation between the serum irisin level and diabetes mellitus needs to be further clarified.
Obesity is regarded as a risk factor for cardiovascular diseases [
32]. Traditional risks factors for cardiovascular disease, such as diabetes mellitus, dyslipidemia and hyperuricemia are more likely to cluster in obese populations. The clustering of CVRFs greatly increases not only the incidence of cardiovascular disease but also the mortality compared with cases with an individual CVRF [
33,
34]. In the present study, we found that the serum irisin level had an inverse association with the number of clustered CVRFs. We further revealed that a high serum irisin level was correlated to a decreased level of clustering of CVRFs among Chinese overweight/obese populations than a low serum irisin level. Consistent with the present study, several previous studies have shown that patients with coronary disease had lower serum irisin levels [
12,
13]. It is well known that atherosclerosis underlies a variety of cardiovascular diseases, and that many CVRFs, including diabetes mellitus, dyslipidemia, smoking and hypertension, can promote the pathogenesis of atherosclerosis. We found that the serum irisin level had an independent relationship with smoking, dyslipidemia and the number of clustered CVRFs. Therefore, we conclude that the serum irisin level may act as a biomarker for the risk of cardiovascular diseases, at least in the overweight/obese population.
Previous studies have demonstrated the possible mechanism by which serum irisin prevents the development of atherosclerosis. In apoE-deficiency-induced atherosclerotic animal models, irisin administration decreases the atherosclerotic plaque area, as well as the inflammation and cell apoptosis observed in aortic tissues [
35,
36]. In human umbilical vein endothelial cells, irisin decreases lipid-induced cell apoptosis and alleviates oxidative stress, which could prevent the occurrence of atherosclerosis [
35‐
37]. Irisin also has effects on metabolism. For example, irisin impacts the metabolism of glucose and lipids [
38‐
40]. Additionally, irisin induces cultured white adipocyte browning, resulting in an increase in energy expenditure and weight loss in high-fat-fed obese mice [
38]. The administration of irisin in high-fat-fed obese mice reduces the expression of hepatic cholesterol genes [
39] and hepatic gluconeogenesis [
40]. In human hepatocellular carcinoma cells with an insulin-resistance state, irisin ameliorates glucose output and fat accumulation [
41]. Taken together, these findings support a notion that irisin offers benefits for cardiovascular diseases.
The limitations of the present study should be acknowledged. First, the sample size of our study was small. Second, this was a cross-sectional study, which was limited to determine the association between serum irisin levels and a single or clustering of CVRFs, and/or cardiovascular diseases, but not the cause-effect correlation. Third, smoking, one of the main CVRFs in our present study, was defined by self-report, which might have introduced a certain level of bias to this study.
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