Subcutaneous Adipose Tissue Macrophage Infiltration Is Associated With Hepatic and Visceral Fat Deposition, Hyperinsulinemia, and Stimulation of NF-κB Stress Pathway

OBJECTIVE-To examine in obese young adults the influence of ethnicity and subcutaneous adipose tissue (SAT) inflammation on hepatic fat fraction (HFF), visceral adipose tissue (VAT) deposition, insulin sensitivity (SI), beta-cell function, and SAT gene expression. RESEARCH DESIGN AND METHODS-SAT biopsies were obtained from 36 obese young adults (20 Hispanics, 16 African Americans) to measure crown-like structures (CLS), reflecting SAT inflammation. SAT, VAT, and HFF were measured by magnetic resonance imaging, and SI and beta-cell function (disposition index [DI]) were measured by intravenous glucose tolerance test. SAT gene expression was assessed using Illumina microarrays. RESULTS-Participants with CLS in SAT (n = 16) were similar to those without CLS in terms of ethnicity, sex, and total body fat. Individuals with CIS had greater VAT (3.7 +/- 1.3 vs. 2.6 +/- 1.6 L; P = 0.04), HFF (9.9 +/- 7.3 vs. 5.8 +/- 4.4%; P = 0.03), tumor necrosis factor-alpha (20.8 +/- 4.8 vs. 16.2 +/- 5.8 pg/mL; P = 0.01), fasting insulin (20.9 +/- 10.6 vs. 9.7 +/- 6.6 mU/mL; P < 0.001) and glucose (94.4 +/- 9.3 vs. 86.8 +/- 5.3 mg/dL; P = 0.005), and lower DI (1,559 +/- 984 vs. 2,024 +/- 829 x 10(-4) min(-1); P = 0.03). Individuals with CLS in SAT exhibited upregulation of matrix metalloproteinase-9 and monocyte antigen CD14 genes, as well as several other genes belonging to the nuclear factor-kappa B (NF-kappa B) stress pathway. CONCLUSIONS-Adipose tissue inflammation was equally distributed between sexes and ethnicities. It was associated with partitioning of fat toward VAT and the liver and altered beta-cell function, independent of total adiposity. Several genes belonging to the NF-kappa B stress pathway were upregulated, suggesting stimulation of proinflammatory mediators. Diabetes 60:2802-2809, 2011