Monocytes from Metabolic Syndrome Subjects Exhibit a Proinflammatory M1 Phenotype

Background: The metabolic syndrome is a highly prevalent state affecting one in three US adults and comprises a cluster of cardiometabolic risk factors. While metabolic syndrome is a proinflammatory state, there is a paucity of studies examining monocyte/macrophage phenotype in metabolic syndrome subjects. This was the aim of this study. Methods: Following informed consent, metabolic syndrome and age- and gender-matched healthy subjects ( n =15/group) were recruited, and monocytes were obtained for phenotypic characterization of the classical M1 phenotype and alternative M2 phenotype. Biomarkers of inflammation, C-reactive protein (CRP), and proinflammatory cytokines were examined. Results: Metabolic syndrome subjects had significantly higher waist circumference (WC), significantly increased systolic blood pressure, higher fasting glucose, triglycerides, and free fatty acids levels, and lower high-density lipoprotein cholesterol (HDL-C) levels compared to matched controls. Also, CRP and endotoxin levels were significantly elevated in metabolic syndrome compared to controls. Metabolic syndrome subjects had significantly higher levels of the M1 phenotype and significantly decreased levels of the M2 phenotype compared to controls, even after adjusting for WC. Among the other biomarkers of inflammation, there were significant increases in the proinflammatory cytokines and chemokines interleukin-1β (IL-1β), IL-6, and monocyte chemoattractant protein-1 (MCP-1) and decreased IL-10 in metabolic syndrome compared to controls. The M1 phenotype was significantly correlated to levels of CRP, endotoxin, MCP-1, and WC and negatively with HDL-C. Conclusions: Monocytes from metabolic syndrome subjects display a proinflammatory M1 phenotype that could promote the increased cardiometabolic burden in these subjects.