Sex Affects Regional Variations in Subcutaneous Adipose Tissue T Cells but not Macrophages in Adults with Obesity

Abstract

ObjectiveThe inflammatory environment in lower‐body subcutaneous adipose tissue (SAT) has been largely unexplored. This study aimed to examine the effects of region (upper body vs. lower body) and sex on SAT immune cell profiles in young adults with obesity.MethodsAbdominal (AB) and femoral (FEM) SAT was collected from 12 males (mean [SEM] age = 30.8 [1.4] years; mean [SEM] BMI = 34.1 [1.1] kg/m2) and 22 females (mean [SEM] age = 30.6 [0.6] years; mean [SEM] BMI = 34.0 [0.7] kg/m2) with obesity via needle aspiration. Flow cytometry was used to quantify macrophage (CD68+) and T‐cell (CD3+) subpopulations in the stromovascular fraction of each SAT region.ResultsFemales had a greater proportion of most T‐cell types (CD3+CD4+CD45RA+, CD3+CD4+CD45RA−, and CD3+CD8+CD45RA+) in FEM compared with AB SAT, while males had similar proportions in both regions. Regardless of sex, the M1‐like macrophage population (CD68+CD206−) was proportionally higher in AB SAT than in FEM SAT.ConclusionsResults showed that T‐cell populations vary by SAT region in females but not males. Both sexes, however, have proportionately more proinflammatory macrophages in upper‐body than in lower‐body SAT. It remains to be seen how these unique immune cell profiles in males and females with obesity contribute to adipose tissue inflammation and metabolic disease risk.

Sex differences in regional adipose tissue depots pose different threats for the development of Type 2 diabetes in males and females

“…In humans, few sex differences in macrophages have so far have been noted. This includes results from our own lab, which found no sex difference in the number of M2 like (CD68+ CD206+) and M1 like (CD68+ CD206−) macrophages per g abdominal or femoral SAT 76 . However, in both sexes, there were greater numbers of M1 like cells (CD68+ CD206−) per g in abdominal versus femoral SAT 76 .…”

“…In humans, the presence of proinflammatory cytotoxic T cells (CD8+) appears greater in the omentum than abdominal SAT in males and females 86 . However, with regard to SAT, we have observed that females have greater T helper (CD4+) and cytotoxic (CD8+) T‐cell subsets in femoral SAT compared with abdominal SAT, whereas in males no differences were found between the two depots 76 …”

“…This includes results from our own lab, which found no sex difference in the number of M2 like (CD68+ CD206+) and M1 like (CD68+ CD206−) macrophages per g abdominal or femoral SAT 76 . However, in both sexes, there were greater numbers of M1 like cells (CD68+ CD206−) per g in abdominal versus femoral SAT 76 . Additionally, another study showed that when examining renal perivascular fat, there were no differences in macrophages (CD14 + [number of cells/g adipose tissue]) between males and premenopausal females 77 .…”

“…Summary of sex differences in the pathogenesis of T2D through examination of regional differences in adipose tissue factors. In female abSAT and fmSAT, there are greater ATM, 77,84 T cells, 76,89 and leptin 15,112,113 compared with males, whereas males have greater hypertrophy 48 and TNFα 151–155 than females. Females also have the protection of greater hyperplasia 48,50–54 and adiponectin 133 secretion from abSAT and fmSAT.…”

“…In males and females, CRP correlates positively with waist circumference (Table 8). 76,119 Within the abdominal depot, VAT, not SAT mass, has been associated with higher CPR in both sexes 170,171 . The greater association between CRP and VAT mass is likley due to VAT's direct drainage of IL6 into the liver, via the portal vein, which stimulates CRP secretion.…”