Macrophage content in subcutaneous adipose tissue: associations with adiposity, age, inflammatory markers, and whole-body insulin action in healthy Pima Indians.
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.


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.
Ortega Martinez de Victoria
Emilio
E
Phoenix 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, USA. eortega1@clinic.ub.es
Xu
Xiaoyuan
X
Koska
Juraj
J
Francisco
Ann Marie
AM
Scalise
Michael
M
Ferrante
Anthony W
AW
Krakoff
Jonathan
J
D050154:Adiposity / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D000328:Adult; D000367:Age Factors; D015703:Antigens, CD / Q000235:genetics; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics; D039481:CD11b Antigen / Q000235:genetics; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007150:Immunohistochemistry; D007198:Indians, North American; D007328:Insulin / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008297:Male; D009765:Obesity / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012737:Sex Factors; D050151:Subcutaneous Fat / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D039481:CD11b Antigen; D007004:Hypoglycemic Agents; D007328:Insulin; D016186:Receptor, Macrophage Colony-Stimulating Factor; C067980:CD68 antigen, human; D000097382:CD68 Molecule