Background and Aims:Metabolic Syndrome (MetS), a global problem, predisposes to an increased risk for type 2 diabetes and premature cardiovascular disease. While MetS is associated with central obesity, there is scanty data on adipocyte hypertrophy, increased fat cell size (FCS), in MetS. The aim of this study was to investigate FCS status in adipose tissue (AT) biopsy of patients with nascent MetS without the confounding of diabetes, cardiovascular disease, smoking, or lipid therapy.Methods and Results:Fasting blood and subcutaneous gluteal AT biopsies were obtained in MetS (n= 20) and controls (n= 19). Cardio-metabolic features, FFA levels, hsCRP, and HOMA-IR were significantly increased in patients with MetS. Waist-circumference (WC) adjusted-FCS was significantly increased in patients with MetS and increased with increasing severity of MetS. Furthermore, there were significant correlations between FCS with glucose, HDL-C, and the ratio of TG: HDL-C. There were significant correlations between FCS and FFA, as well as endotoxin and monocyte TLR4 abundance. Additionally, FCS correlated with readouts of NLRP3 Inflammasome activity. Most importantly, FCS correlated with markers of fibrosis and angiogenesis.Conclusions:In conclusion, in patients with nascent MetS, we demonstrate WC-adjusted increase in FCS from gluteal adipose tissue which correlated with cellular inflammation, fibrosis, and angiogenesis. While these preliminary observations were in gluteal fat, future studies are warranted to confirm these findings in visceral and other fat depots.