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Macrophage Infiltration into Omental Versus Subcutaneous Fat across Different Populations: Effect of Regional Adiposity and the Comorbidities of Obesity

Diabetes Unit and Internal Medicine C (I.H.-B.), Pathology Institute (H.R., N.S.-V.), and Surgery Department A (E.A.), Soroka Medical Center, Beer-Sheva 84101, Israel; Medical Department III (M.B., N.K., M.S.), University of Leipzig, 04109 Leipzig, Germany; and The National Institute of Biotechnology in The Negev (S.O.), The Department of Clinical Biochemistry (S.O., N.B., A.R.), Department of Epidemiology (I.S.), and the S. Daniel Abraham Center for Health and Nutrition (I.S., A.R.), Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84103, Israel

Address all correspondence and requests for reprints to: Assaf Rudich, M.D., Ph.D., Department of Clinical Biochemistry, Faculty of Health Sciences, Ben-Gurion University, Beer-Sheva 84103, Israel. E-mail: rudich{at}bgu.ac.il.

Context: Macrophage infiltration into adipose tissue has been demonstrated to accompany obesity, with a potential preferential infiltration into intraabdominal vs. sc fat.

Objective: Our objective was to determine whether this occurs across different populations with a range of body mass indexes and to assess the relationship with regional adiposity and comorbidity of obesity.

Setting and Patients: In two independent cohorts, we used paired omental (OM) and sc fat biopsies from lean controls or predominantly sc or intraabdominally obese persons with minimal comorbidity (n = 60, cohort 1), or from severely obese women with a significant rate of comorbidity (n = 29, cohort 2).

Results: Elevated macrophage infiltration into OM vs. sc fat was observable in lean subjects and exaggerated by obesity, particularly if predominantly intraabdominal. This was paralleled by increased monocyte chemoattractant protein-1 (MCP1) and colony-stimulating factor-1 (CSF1) mRNA levels. Level of CSF1 and MCP1 mRNA correlated with the number of OM macrophages (r = 0.521, P < 0.0001 and r = 0.258, P < 0.051, respectively). In severely obese women (mean body mass index = 43.0 ± 1.1 kg/m²), higher protein expression of both MCP1 and CSF1 was detected in OM vs. sc fat. Number of OM macrophages, but not of sc macrophages, correlated with waist circumference (r = 0.636, P = 0.001 vs. r = 0.170, P = 0.427) and with the number of metabolic syndrome parameters (r = 0.385, P = 0.065 vs. r = –0.158, P = 0.472, respectively). Preferential macrophage infiltration into OM fat was mainly observed in a subgroup in whom obesity was associated with impaired glucose homeostasis.

Conclusions: Preferential macrophage infiltration into OM fat is a general phenomenon exaggerated by central obesity, potentially linking central adiposity with increased risk of diabetes and coronary heart disease.

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