Abstract
Inflammation plays a central role in the pathogenesis of metabolic syndrome (MetS). Cyclophilin B (CypB) can be constitutively secreted in response to inflammatory stimuli and oxidative stress, participating in tissue or systemic inflammation. We investigated the relationship between CypB and MetS in both humans and mice. Serum CypB levels were determined in 211 subjects with MetS and 292 subjects without MetS (non-MetS) (133 healthy controls and 159 high-risk subjects with one to two MetS components). Additionally, CypB expression in metabolic organs was examined in mice fed with high-fat diet (HFD) and genetically obese (ob/ob) mice. Serum CypB level was significantly higher in MetS subjects compared with both groups of non-MetS subjects (193.80 ± 83.22 vs. 168.38 ± 65.01 vs. 124.26 ± 47.83 ng/mL, P < 0.001). Particularly, serum CypB level was significantly higher in subjects with hypertension, central obesity, diabetes mellitus or hyperglycemia, elevated levels of triglycerides, or reduced levels of high-density lipoprotein than in those without. Moreover, CypB was positively associated with the number of MetS components (r = 0.404, P < 0.001), indicating that a higher serum CypB level reflected more severe MetS. Multivariate regression revealed that a one SD increase in CypB was associated with an odds ratio of 1.506 (1.080-2.101, P = 0.016) for MetS prevalence after adjusting for age, gender, conventional risk factors, and medication. Stratified analyses by age and gender demonstrated that subjects >60 years old with higher CypB levels were more likely to have MetS, and the risk for MetS was higher and more significant in women compared with men. Additionally, CypB expression levels were lower at baseline and dramatically enhanced in metabolic organs (such as the liver) and visceral and subcutaneous adipose tissue from HFD-induced obese mice and ob/ob mice. Increased CypB levels were significantly and independently associated with the presence and severity of MetS, indicating that CypB could be used as a novel biomarker and clinical predictor of MetS.
Highlights
As a cluster of cardiovascular risk factors, metabolic syndrome (MetS) consists of multiple metabolic abnormalities including central obesity, impaired fasting blood glucose or insulin resistance, dyslipidemia, and hypertension [1]
Accumulating evidence including ours has demonstrated that inflammation and immune response play an essential role in lipid metabolism, insulin resistance, obesity, and MetS development, and some related factors were found to be of vital importance with diagnostic and prognostic value or as therapeutic targets [5,6,7]
Serum cyclophilin B (CypB) Level Was Associated with the Prevalence and Severity of MetS
Summary
As a cluster of cardiovascular risk factors, metabolic syndrome (MetS) consists of multiple metabolic abnormalities including central obesity, impaired fasting blood glucose or insulin resistance, dyslipidemia, and hypertension [1]. It has become a major public health problem worldwide, having a critical role in the origin of several cardiometabolic diseases such as cardiovascular disease and type 2 diabetes mellitus (DM) [1, 2] and being associated with an increased risk of developing certain types of cancer [3]. High levels of extracellular cyclophilins have been detected in several human inflammatory diseases such as severe sepsis, vascular smooth muscle cell disease, atherosclerosis, lupus, and rheumatoid arthritis, playing an important role in regulating the inflammatory process [11]
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