Background: Adipose tissue inflammation is linked to adipose tissue insulin resistance. However, whether this is a causal relationship remains controversial. Therefore, we aimed to explore the relationship between measures of adipose tissue inflammation and adipose tissue insulin sensitivity over a wide range of body fat distribution and adipose tissue insulin sensitivity.
Methods: We recruited a total of 87 volunteers (30 men and 57 women). Adipose tissue insulin sensitivity was quantified as the insulin concentration required for a 50% suppression of lipolysis (IC50). Lipolysis was measured as steady-state palmitate flux before and during a hyperinsulinemic-euglycemic clamp. Adipose tissue macrophage (ATM) was quantified by immunohistochemistry with antibodies against CD68 (total ATM), CD14 (pro-inflammatory ATM) and CD206 (anti-inflammatory ATM) and senescent preadipocyte content was quantified by β-galactosidase positivity using fluorescent microscopy in abdominal and femoral fat biopsies.
Results: Total ATM content was only weakly associated with IC50 in abdominal fat (r=0.26, p=0.01) and no association was observed for femoral fat. No association was observed between IC50 and pro-inflammatory ATM content. Anti-inflammatory ATM content was associated with IC50 in abdominal (r=0.46, p<0.001) and femoral (r=0.33, p=0.02) fat. Senescent preadipocyte content was weakly associated with IC50 in femoral fat (r=0.36, p=0.01), but no association was observed in abdominal fat. Fat cell size was strongly associated with IC50 in both abdominal (r=0.6 p<0.001) and femoral (r=0.48, p<0.01) fat.
Conclusions: ATM content is only weakly associated to adipose tissue insulin sensitivity. Only the content of anti-inflammatory, not pro-inflammatory macrophages, was associated with adipose tissue insulin sensitivity. This argues against pro-inflammatory macrophages as mediators of insulin resistance in adipose tissue.
E. Søndergaard: None. A.E. Espinosa De Ycaza: None. M. Morgan-Bathke: None. K. Lytle: None. D.A. Delivanis: None. B.G. Carranza Leon: None. M.D. Jensen: None.
National Institutes of Health (DK40404, DK45343)