2094-P: Decreased Human Adipose Tissue-Resident Eosinophils in Obese Subjects Is Associated with Increased Insulin Resistance

Eosinophils (EOS) have been shown to play a major role in animal adipose tissue (AT) metabolism by promoting insulin sensitivity (IS) through an increase in alternatively activated macrophages (M2). Additionally, AT EOS are known to be decreased in obese mice. Currently, translational evidence is lacking for the role of EOS in human AT metabolism and IS. We investigated whether human AT-resident EOS numbers, as in animal models, are decreased in obese subjects and correlate with their degree of insulin resistance (IR). To date, we have studied 16 lean subjects (F15/M1, age 43 +2 years old; BMI 22.5+0.4kg/m²; HOMA-IR: 0.99 +0.38) and 22 obese, IR subjects (17F/5M, age 42 +1.3 years old; BMI: 38.9 +1.0kg/m²; HOMA-IR:5.0 +1.6) undergoing elective laparoscopic surgery. During surgical procedure, subcutaneous (SC) and omental (OM) fat was harvested. Stromal vascular fraction (SVF) was isolated after collagenase digestion of the fat samples. SVF was subjected to FACS analysis using BD Biosciences FACSAria III Cell Sorter with EOS count normalized as percent of CD45+ cells. Viable EOS were isolated and cytospin preparation was stained with a Diff-Quik. EOS isolated from SC AT of lean(L) subjects were found to significantly outnumber those obtained from obese (Ob) subjects by a 2.1:1 ratio (SC L:2.34 +0.29 vs. SC Ob: 1.11 +0.21, P<0.03). A similar, but non-significant, trend was observed in OM. Furthermore, the number of SC AT-EOS was significantly inversely correlated with BMI, % fat and QUICKI index. qPCR analysis of SC AT mRNA revealed significantly increased classically activated macrophage markers (M1) (IL-1, IL-6, TNFα) in Ob vs. L, respectively while M2 markers (ARG-1, CCL24, CCL26) were significantly decreased in Ob vs. L. Based on these results we propose that, as in animal models, AT-resident EOS mediate AT metabolism and potentially IS by preserving an anti-inflammatory milieu within lean AT. Further studies are needed to elucidate the mechanism(s) involved.