ABSTRACT: Objectives: We compared metabolic biomarkers in the blood and PBMC gene expression profiles among normal weight, mildly obese, and moderately obese Korean adult men. Design: Subjects were classified as normal weight (BMI, 18.5~23 kg/m2), mildly obese (BMI, 25~27.5 kg/m2), and moderately obese (BMI, 27.5~30 kg/m2). Results: High leptin, lipids (except LDL- and HDL-cholesterol), and apolipoprotein B levels and low adiponectin and HDL-cholesterol levels were present in the plasma of both mildly and moderately obese subjects. Circulating levels of inflammatory cytokines (TNF-α and IL-6) and markers of insulin resistance, oxidative stress, and liver damage were altered in moderately obese subjects but not mildly obese subjects. PBMC transcriptome data showed enrichment of pathways involved in energy metabolism, insulin resistance, bone metabolism, cancer, inflammation, and fibrosis in both mildly and moderately obese subjects. Signaling pathways involved in oxidative phosphorylation; triglyceride synthesis; carbohydrate metabolism; insulin, mTOR, FOXO, RAP1, RAS, and TGF-β signaling; and ECM–receptor interaction were enriched only in moderately obese subjects, indicating that changes in PBMC gene expression profiles according to metabolic disturbances were associated with the development and/or aggravation of obesity. In particular, upregulation of 8 genes (FLT3LG, LTB, IL23A, CD19, CPT1B, AXIN2, CACNA1L, RPRM) and downregulation of 2 genes (CCL4L1, LPAR5) were observed only in mildly obese subjects. Six genes (CXCR5, NFKBIA, BIRC3, TNFAIP3, DDIT3, PDE4B) and 4 genes (CX3CR1, HSPA1A, CACNA2D3, APAF1) were up- and down-regulated, respectively, in both mildly and moderately obese subjects. These results suggested that these genes could be used as early or stable biomarkers for diagnosing and treating obesity-associated metabolic disturbance.
