Macrophage Content in Subcutaneous Adipose Tissue

Associations With Adiposity, Age, Inflammatory Markers, and Whole-Body Insulin Action in Healthy Pima Indians

  1. Emilio Ortega Martinez de Victoria1,
  2. Xiaoyuan Xu2,
  3. Juraj Koska1,
  4. Ann Marie Francisco2,
  5. Michael Scalise2,
  6. Anthony W. Ferrante, Jr.2 and
  7. Jonathan Krakoff1
  1. 1Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Phoenix, Arizona
  2. 2Naomi Berrie Diabetes Center, Columbia University, New York, New York
  1. Corresponding author: Emilio Ortega Martinez de Victoria, mailto:eortega1{at}clinic.ub.es

Abstract

OBJECTIVE— In severely obese individuals and patients with diabetes, accumulation and activation of macrophages in adipose tissue has been implicated in the development of obesity-associated complications, including insulin resistance. We sought to determine whether in a healthy population, adiposity, sex, age, or insulin action is associated with adipose tissue macrophage content (ATMc) and/or markers of macrophage activation.

RESEARCH DESIGN AND METHODS— Subcutaneous ATMc from young adult Pima Indians with a wide range of adiposity (13–46% body fat, by whole-body dual-energy X-ray absorptiometry) and insulin action (glucose disposal rate 1.6–9 mg/kg estimated metabolic body size/min, by glucose clamp) were measured. We also measured expression in adipose tissue of factors implicated in macrophage recruitment and activation to determine any association with ATMc and insulin action.

RESULTS— ATMc, as assessed by immunohistochemistry (Mphi) and by macrophage-specific gene expression (CD68, CD11b, and CSF1R), were correlated with percent body fat, age, and female sex. Gene expression of CD68, CD11b, and CSF1R but not Mphi was correlated negatively with glucose disposal rate but not after adjustment for percent body fat, age, and sex. However, adipose tissue expression of plasminogen activator inhibitor type-1 (PAI-1) and CD11 antigen-like family member C (CD11c), markers produced by macrophages, were negatively correlated with adjusted glucose disposal rate (r = −0.28, P = 0.05 and r = −0.31, P = 0.03).

CONCLUSIONS— ATMc is correlated with age and adiposity but not with insulin action independent of adiposity in healthy human subjects. However, PAI-1 and CD11c expression are independent predictors of insulin action, indicating a possible role for adipose tissue macrophage activation.

Footnotes

  • Published ahead of print at http://diabetes.diabetesjournals.org on 13 November 2008.

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    • Accepted November 8, 2008.
    • Received April 22, 2008.
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