Abstract 10252: Differences in the Transcriptomic Profile of Visceral Fat in Persons With Metabolically “Healthy” versus Metabolically “Unhealthy” Obesity

Introduction: There is varied metabolic dysfunction among persons with obesity. We assessed differences in visceral adipose tissue transcriptome between persons with metabolically healthy and metabolically unhealthy obesity. Methods: We studied 40 patients with obesity (mean age 46; median body mass index 46 kg/m 2 ) undergoing bariatric surgery at Geisinger Medical Center. Three obesity groups were defined. Two (metabolically unhealthy) had metabolic syndrome (MetS) with diabetes (DM) (MUOD; n=16) or without DM (MUO; n=8). The third (metabolically healthy) had no MetS or DM (MHO, n=16). Omental adipose tissue obtained at bariatric surgery was snap frozen. Total RNA was extracted and RNA sequencing performed using an Illumina platform. Differential gene expression between the 3 groups was analyzed using DESeq2 software and pathway enrichment analysis performed using Gene Ontology. Results: Using an adjusted P-value <0.05, 134 genes were upregulated and 114 genes downregulated in patients with MUOD versus MHO. Genes with the highest amplitude of transcriptional differences included lipopolysaccharide binding protein with log2 fold change (l2fc) of 2.2 and Padj= 1.6 10 -7 , osteopontin (l2fc= 1.9, Padj=1.6 10 -7 ), chitinase 3 L1 (l2fc= 2.4 Padj= 1.7 10 -4 ), carbonic anhydrase 3 (l2fc= -2.6 Padj= 4.8 10 -8 ) and perilipin 5 (l2fc= -1.2 Padj= 0.003). GO upregulated pathways were enriched for pro-inflammatory pathways including leukocyte migration, responses to lipopolysaccharide and interleukin-1, and T cell activation (Padj= 1.7 10 -13 , 9.89 10 -11 , 4.9 10 -09 , 1.1 10 -08 respectively). Downregulated pathways were enriched in organic acid catabolic process, fatty acid oxidation and oxidative phosphorylation (Padj= 7.7 10 -20 , 8.6 10 -20 , 1.5 10 -09 respectively). An inflammatory signature was also present in MUO compared to MHO, whereas oxidative processes were not downregulated in those with MUO relative to MHO. Conclusion: In patients with class III obesity, we found a heterogeneous visceral adipose tissue transcriptome. A pro-inflammatory signature in visceral fat was found across the metabolic syndrome spectrum. A metabolic signature with decreased oxidative phosphorylation was linked to metabolic syndrome with concomitant diabetes.