1768-P: Inflammation in Visceral and Subcutaneous Fat and Human Insulin Resistance

Abstract

Background/Methods: Visceral adipose tissue (VAT) is associated with increased risk for T2D and CVD. This depot, which accounts for only 5-10% of total fat mass, may play a relatively important role in determining insulin resistance (IR) due to its proximity to gut lymphatics and liver. Immune cells in fat respond to adipocyte stress and bacterial antigens from the gut with cytokine release, adversely affecting hepatic and systemic glucose metabolism. Few human studies have examined inflammation in VAT with regard to systemic IR. We hypothesized that inflammation in VAT vs. SAT would be associated with IR. To test this hypothesis we recruited 25 nondiabetic bariatric surgery patients who underwent whole-body insulin sensitivity testing via steady-state plasma glucose (SSPG) test prior to surgery. Samples of SAT and VAT were harvested for collagenase digestion and flash freezing for flow cytometry and gene expression. Results/Conclusion: The cohort was 80% female, 20% male, age 48±10 years, BMI 43.7±6.1 kg/m2, fasting glucose 103±15 mg/dL. IR was defined as SSPG > 200, and IS as SSPG < 160 mg/dL. Comparison of immune cell profiles revealed greater frequency of macrophages in both SAT and VAT in IR vs. IS subjects, and higher expression of proinflammatory marker CD44 in IR vs. IS subjects. Macrophage number and phenotype (M1, M2, CD44+) did not differ between depots, suggesting systemic rather than localized inflammation contributes to IR. Disclosure T. McLaughlin: Advisory Panel; Self; January. Stock/Shareholder; Self; Eiger BioPharmaceuticals. E.J. Zanley: None. C.I. Petlura: None. L.L. Tolentino: None. O. Choi: None. J. Chuang: None. J. Morton: None. Funding American Heart Association