Subcutaneous adipose tissue macrophage infiltration is associated with hepatic and visceral fat deposition, hyperinsulinemia, and stimulation of NF-κB stress pathway

Diabetes. 2011 Nov;60(11):2802-9. doi: 10.2337/db10-1263.

Abstract

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.

Trial registration: ClinicalTrials.gov NCT00697580.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Cross-Sectional Studies
  • Fatty Liver / etiology*
  • Female
  • Humans
  • Hyperglycemia / etiology
  • Hyperinsulinism / etiology*
  • Inflammation Mediators / metabolism
  • Insulin Resistance
  • Insulin-Secreting Cells / metabolism
  • Intra-Abdominal Fat / pathology*
  • Liver / metabolism
  • Liver / pathology
  • Macrophages / immunology
  • Macrophages / pathology*
  • Male
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Obesity / blood
  • Obesity / immunology
  • Obesity / pathology*
  • Obesity / physiopathology
  • Oligonucleotide Array Sequence Analysis
  • Subcutaneous Fat / immunology
  • Subcutaneous Fat / metabolism
  • Subcutaneous Fat / pathology*
  • Up-Regulation
  • Young Adult

Substances

  • Inflammation Mediators
  • NF-kappa B

Associated data

  • ClinicalTrials.gov/NCT00697580