228-OR: Differential Expression of miRNA in Human Subcutaneous and Visceral Adipose Tissue Is Related to Insulin Resistance

Abstract

Introduction: Obesity is related to insulin resistance (IR) but not all obese individuals are IR. Differences in regional fat distribution and function contribute to the metabolic heterogeneity of obesity. miRNA is known to regulate mRNA and may play a role in mediating IR by modifying adipose tissue function. We tested the hypothesis that miRNA in human visceral (VAT) and subcutaneous (SAT) fat would be differentially expressed in individuals who were classified as insulin sensitive (IS) or IR. Methods: 12 participants, classified as IR or IS (top 40 percentile) via steady-state plasma glucose (SSPG) test, were recruited from the Stanford Bariatric Surgery Clinic. Tissue samples (SAT and VAT) were harvested from the greater momentum during bariatric surgery. Total RNA was extracted with QIAGEN RNeasy® Lipid Tissue Mini Kit. The miRNA experiment used QuantStudio™ 12K Flex OpenArray® microRNA Starter Kit with modifications by adding Ath-miR-159a spike-in, and use of SuperScript VILO cDNA Synthesis Kit. Data analysis done via Applied Biosystems™ Relative Quantitation Analysis. miRNA comparisons with fold-change <0.5 or >2 and p<0.were considered statistically significant. Known target genes of significant miRNA were quantified via RT-PCR from tissue samples. Results: Differential expression in VAT vs. SAT showed one upregulated (miR-885-5p) and 12 downregulated miRNAs. In SAT, for IR vs. IS individuals showed 12 upregulated miRNA, while in VAT, IR vs. IS included one upregulated (miR-30c) and downregulated miRNA. Conclusion: In VAT relative to SAT, miR-885-5p was a significant predictor of fatty liver and majority of downregulated miRNA (miR-335, 196b, 497, 22, 106b, 340) reduced lipogenesis and increased insulin signaling. In IR vs. IS of SAT, majority of miRNA reduced insulin sensitivity (miR-146b, 29c, 502-3p) . For IR vs. IS of VAT, miR-30c promoted adipocyte differentiation and majority of downregulated miRNA increased insulin sensitivity (miR-106b, 24, 143, 340) . Disclosure N.Saini: None. A.Deng: None. H.Chen: None. Y.Xu: None. P.S.Tsao: None. T.Mclaughlin: Board Member; January, Inc., Research Support; Merck & Co., Inc., Novo Nordisk, Stock/Shareholder; Eiger BioPharmaceuticals.