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

• Published in: Diabetes (New York, N.Y.) Vol. 60; no. 11; pp. 2802 - 2809
• Main Authors: Lê, Kim-Anne, Mahurkar, Swapna, Alderete, Tanya L., Hasson, Rebecca E., Adam, Tanja C., Kim, Joon Sung, Beale, Elizabeth, Xie, Chen, Greenberg, Andrew S., Allayee, Hooman, Goran, Michael I.
• Format: Journal Article
• Language: English
• Published: United States American Diabetes Association 01.11.2011
• Subjects: Adipose tissues; Adolescent; Adult; Cross-Sectional Studies; Fatty Liver - etiology; Female; Gene expression; Genetic aspects; Humans; Hyperglycemia - etiology; Hyperinsulinism - etiology; Inflammation Mediators - metabolism; Insulin Resistance; Insulin-Secreting Cells - metabolism; Intra-Abdominal Fat - pathology; Liver - metabolism; Liver - pathology; Macrophages; Macrophages - immunology; Macrophages - pathology; Male; Metabolic diseases; NF-kappa B - genetics; NF-kappa B - metabolism; Obesity - blood; Obesity - immunology; Obesity - pathology; Obesity - physiopathology; Obesity Studies; Oligonucleotide Array Sequence Analysis; Physiological aspects; Risk factors; Subcutaneous Fat - immunology; Subcutaneous Fat - metabolism; Subcutaneous Fat - pathology; Up-Regulation; Young Adult; United States
• ISSN: 0012-1797; 1939-327X; 1939-327X
• DOI: 10.2337/db10-1263

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), β-cell function, and SAT gene expression. 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 β-cell function (disposition index [DI]) were measured by intravenous glucose tolerance test. SAT gene expression was assessed using Illumina microarrays. Participants with CLS in SAT (n = 16) were similar to those without CLS in terms of ethnicity, sex, and total body fat. Individuals with CLS 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-α (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 × 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-κB (NF-κB) stress pathway. Adipose tissue inflammation was equally distributed between sexes and ethnicities. It was associated with partitioning of fat toward VAT and the liver and altered β-cell function, independent of total adiposity. Several genes belonging to the NF-κB stress pathway were upregulated, suggesting stimulation of proinflammatory mediators.