Reduced Adipose Tissue Oxygenation in Human Obesity

Evidence for Rarefaction, Macrophage Chemotaxis, and Inflammation Without an Angiogenic Response

  1. Magdalena Pasarica,
  2. Olga R. Sereda,
  3. Leanne M. Redman,
  4. Diana C. Albarado,
  5. David T. Hymel,
  6. Laura E. Roan,
  7. Jennifer C. Rood,
  8. David H. Burk and
  9. Steven R. Smith
  1. From the Pennington Biomedical Research Center, Baton Rouge, Louisiana
  1. Corresponding author: Steven R. Smith, smithsr{at}pbrc.edu

Abstract

OBJECTIVE— Based on rodent studies, we examined the hypothesis that increased adipose tissue (AT) mass in obesity without an adequate support of vascularization might lead to hypoxia, macrophage infiltration, and inflammation.

RESEARCH DESIGN AND METHODS— Oxygen partial pressure (AT pO2) and AT temperature in abdominal AT (9 lean and 12 overweight/obese men and women) was measured by direct insertion of a polarographic Clark electrode. Body composition was measured by dual-energy X-ray absorptiometry, and insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp. Abdominal subcutaneous tissue was used for staining, quantitative RT-PCR, and chemokine secretion assay.

RESULTS— AT pO2 was lower in overweight/obese subjects than lean subjects (47 ± 10.6 vs. 55 ± 9.1 mmHg); however, this level of pO2 did not activate the classic hypoxia targets (pyruvate dehydrogenase kinase and vascular endothelial growth factor [VEGF]). AT pO2 was negatively correlated with percent body fat (R = −0.50, P < 0.05). Compared with lean subjects, overweight/obese subjects had 44% lower capillary density and 58% lower VEGF, suggesting AT rarefaction (capillary drop out). This might be due to lower peroxisome proliferator–activated receptor γ1 and higher collagen VI mRNA expression, which correlated with AT pO2 (P < 0.05). Of clinical importance, AT pO2 negatively correlated with CD68 mRNA and macrophage inflammatory protein 1α secretion (R = −0.58, R = −0.79, P < 0.05), suggesting that lower AT pO2 could drive AT inflammation in obesity.

CONCLUSIONS— Adipose tissue rarefaction might lie upstream of both low AT pO2 and inflammation in obesity. These results suggest novel approaches to treat the dysfunctional AT found in obesity.

Footnotes

  • Published ahead of print at http://diabetes.diabetesjournals.org on 15 December 2008.

    Clinical trials reg. no. NCT00704197, clinicaltrials.gov.

    Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted December 9, 2008.
    • Received August 11, 2008.
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  1. Diabetes vol. 58 no. 3 718-725
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