Elevated Serum Cyclophilin B Levels Are Associated with the Prevalence and Severity of Metabolic Syndrome

Abstract

ObjectiveInflammation 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.MethodsSerum 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.ResultsSerum 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.ConclusionIncreased 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.

Distribution of ACE2, CD147, CD26, and other SARS‐CoV‐2 associated molecules in tissues and immune cells in health and in asthma, COPD, obesity, hypertension, and COVID‐19 risk factors

“…Viruses integrate cyclophilin A and cyclophilin B in their virions and further can bind and either infect cells via CD147 or activate CD147 signaling 10‐12 . We found that expression of both cyclophilins ( PPIA and PPIB ) is increased in subjects with hypertension and obesity and PPIA correlated positively with BMI in the whole blood, which is confirmed in other studies 64 . In addition, nsp1 protein of SARS‐CoV binds to CD147 via cyclophilins and reduces interferon responses 24 in infected cells.…”

Cyclophilins in Ischemic Heart Disease: Differences Between Acute and Chronic Coronary Artery Disease Patients

“…CypB has a crucial role against ROS and pro-inflammatory status, and their levels were associated with metabolic syndrome, vascular function and heart failure [ 2 , 6 ]. Even though, in our study, we do not find any difference between CAD patients and controls in CypB levels.…”

“…Cyps are some of the most conserved proteins present in eukaryotes and prokaryotes, and they have been implicated in diverse cellular processes and responses to multiple biotic and abiotic stresses [ 3 ]. Some of these proteins, such as CypA, CypB, CypD or FKBP51, have been previously associated with CAD [ 4 - 6 ].…”

Cyclophilin inhibition as a potential treatment for nonalcoholic steatohepatitis (NASH)

“…In another study, genetic knockout of Cyp A decreased adipocyte size and fat mass in mice fed a normal diet, and reduced the weight of mice administered a high fat diet [116]. Cyclophilin B (Cyp B) also is pro-inflammatory when secreted, and serum levels of Cyp B are elevated in HFD-fed mice and in people with metabolic syndrome compared to healthy controls [117].…”

“…Cyclophilin B, predominantly an ER protein, is also secreted in certain injury states by unknown mechanisms. Serum levels of Cyp A or B are elevated in many disease states including NAFLD, NASH, metabolic syndrome, and type 2 diabetes [113][114][115]117,[187][188][189][190][191][192]. In the extracellular milieu cyclophilins act both as leukocyte chemoattractants and as pro-inflammatory cytokines by binding to the transmembrane receptor, CD147 (EMMPRIN), and perhaps other receptors on granulocytes, monocytes, and CD4 T cells [193][194][195][196][197].…”