Subcutaneous Adipose Tissue Macrophage Infiltration Is Associated With Hepatic and Visceral Fat Deposition, Hyperinsulinemia, and Stimulation of NF-κB Stress Pathway
- Kim-Anne Lê1,
- Swapna Mahurkar1,
- Tanya L. Alderete1,
- Rebecca E. Hasson1,
- Tanja C. Adam1,
- Joon Sung Kim1,2,
- Elizabeth Beale3,
- Chen Xie4,
- Andrew S. Greenberg4,
- Hooman Allayee1 and
- Michael I. Goran1⇓
- 1Department of Preventive Medicine, Childhood Obesity Research Center, University of Southern California, Los Angeles, California
- 2Department of Pediatrics, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea
- 3Department of Internal Medicine/Division of Endocrinology and Diabetes, Keck School of Medicine, University of Southern California, Los Angeles, California
- 4Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Tufts University School of Medicine, Boston, Massachusetts
- Corresponding author: Michael I. Goran, .
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), β-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 β-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 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.
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 β-cell function, independent of total adiposity. Several genes belonging to the NF-κB stress pathway were upregulated, suggesting stimulation of proinflammatory mediators.
- Received September 7, 2010.
- Accepted May 26, 2011.
- © 2011 by the American Diabetes Association.
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