Lipodystrophy and obesity are associated with decreased number of T cells with regulatory function and pro-inflammatory macrophage phenotype

BACKGROUND/OBJECTIVES: In lipodystrophy (LD) adipose tissue function to store lipids is impaired, leading to metabolic syndrome, similar to that found in obesity. Emerging evidence links dysmetabolism with disorders of the immune system. Our aim is to investigate whether T-cell populations with regulatory function and monocyte-derived macrophages (MDMs) are affected by LD and obesity. SUBJECTS/METHODS: Blood was collected from 16 LD, 16 obese (OB, BMI430 kg m(-2)) and 16 healthy normal-weight women (CNT). Physical parameters, plasma lipid profile, glucose, HbA1c, leptin levels were determined. Flow cytometry was employed to assess the number of circulating CD4(+)/CD25(hi) regulatory T cells (Tregs) and invariant natural killer T (iNKT) cells. Characterization of MDMs included: 1. morphological/oil-Red-O staining analyses to define two morphotypes: lipid laden (LL) and spindle-like (sp) MDM; 2. gene expression studies; 3. use of conditioned medium from MDMs (MDMs CM) on human SGBS cells. RESULTS: As compared to CNT, LD and, to a lesser extent, obesity were associated with reduced Tregs and iNKTs (P < 0.001 and P < 0.01 for LD and OB, respectively), higher number of LL-MDMs (P < 0.001 and P < 0.01 for LD and OB, respectively), lower number of sp-MDMs (P < 0.001 for both LD and OB), which correlated with increased paracrine stimulation of lipid accumulation in cells (P < 0.001 and P < 0.01 for LD and OB, respectively). LD MDMs showed decreased and increased expression for anti-inflammatory (IL10 and CD163) and pro-inflammatory (CD68 and CCL20) marker genes, respectively. Analysis of correlation indicated that Tregs are directly related with HDL (P < 0.01) and inversely related with LL-MDM (P < 0.001) and that LL-MDM are directly related with triglycerides (P < 0.01) and oxidized LDL (P < 0.01). CONCLUSIONS: LD and obesity are associated with changes in the immune system: a significant reduction in the number of T cells with regulatory function and a shift of MDM towards lipid accumulation. Lipid profile of the patients correlates with these changes.