Intra-abdominal adipose depot variation in adipogenesis, lipogenesis, angiogenesis, and fibrosis gene expression and relationships with insulin resistance and inflammation in premenopausal women with severe obesity

Although severe obesity is associated with insulin resistance (IR) and inflammation, secretory function of intra-abdominal adipose tissues and their relationships with IR and inflammation markers remain poorly understood. Aims were to measure gene expression of adipogenic (C/EBPα/β, PPARγ-1/2, SREBP-1c, LXRα), lipogenic (SCD1, DGAT-1/2), angiogenic (VEGFα, leptin), and fibrotic (LOX, COL6A3) factors in the round ligament (RL), omental (OM), and mesenteric (ME) fat depots and to evaluate their relationships with IR and inflammation markers in 48 women with severe obesity undergoing bariatric surgery. Gene expression was assessed by RT-qPCR, and plasma glucose and insulin (HOMA-IR calculated), PAI-1, IL-6, TNFα, adiponectin, and leptin levels were determined. C/EBPβ and PPARγ-1/2 mRNA levels were more expressed in the OM (0.001<p<0.05). ME showed the highest expression of C/EBPα, SREBP-1c, DGAT-2, and leptin and the lowest of SCD1, LXRα, VEGFα, and LOX (0.001<p<0.05). COL6A3 expression was higher in the ME and RL (p<0.001). COL6A3 expression was negatively associated with IR indices in the RL (0.01<p<0.05) and with fasting glycemia and HOMA-IR in the OM (0.001<p<0.05). VEGFα expression was positively related to TNFα and PAI-1 in the RL (0.001<p<0.05) and to PAI-1 in the OM (p<0.05) and negatively to PAI-1 in the ME (p<0.001). Fibrosis gene expression correlated negatively with inflammation in RL and OM (0.001<p<0.05) and positively with PAI-1 in the ME (0.001<p<0.05). The varying relationships of gene expression profiles with selected IR indices and inflammation biomarkers further suggest these fat depots have distinct contributions to overall health in premenopausal women with severe obesity.