Background: Studies of changes in adipose tissue (AT) inflammation after weight loss have conflicting results. Our aim was to evaluate the changes in AT macrophages, senescence and AT insulin resistance after weight loss.
Methods: Twenty-five participants (18 women) with obesity underwent a lifestyle intervention weight loss program and abdominal-femoral AT biopsies. AT insulin resistance was estimated calculating the insulin concentration that suppresses lipolysis by 50% (IC50) during a hyperinsulinemic-euglycemic clamp. Immunohistochemistry was used to estimate total adipose tissue macrophage (ATM) content (CD68+), pro-inflammatory ATM (CD14+), anti-inflammatory ATM (CD206+). Senescent cells in AT were identified by senescence associated β-galactosidase staining. All parameters were assessed before and after weight loss.
Results: Median BMI was 34 kg/m2 (IQR, 32-35). A median percent weight loss of 10.2% (IQR, 6.5-12.1) resulted in a mean IC50 reduction of -6.2 ± 13 µIU/mL, p=0.03. There was no significant change in ATM content in the abdominal or femoral fat depots after weight loss, except for an increase in CD68 ATMs (mean change 4.5 ± 7.1 ATM/100 adipocytes, P=0.02) in the femoral depot. The proportion of senescent pre-adipocytes in abdominal and femoral depots remained unchanged after weight loss. In the abdominal depot, there was no relationship between IC 50 and CD68 or CD206 ATMs after weight loss, R2= 0.11, P=0.15 and R2= 0.08, P =0.22, for CD68 and CD206 ATMs respectively. There was a weak negative relationship between CD14 ATMs and IC 50 (R2=0.2, P =0.04). In the femoral depot, there was a weak negative relationship between IC 50 and CD68 ATMs (R2=0.23, P=0.04), and no relationship between IC 50 and CD14 ATMs (R2= 0.2, P=0.06) or CD206 ATMs after weight loss (R2= 0.06, P=0.33).
Conclusion: Moderate weight loss is not associated with reduction in ATM content or senescent pre-adipocytes, despite an improvement in AT insulin resistance. Our results suggest that recruitment of some populations of ATMs increases after weight loss.
A.E. Espinosa De Ycaza: None. E. Søndergaard: None. M. Morgan-Bathke: None. D.A. Delivanis: None. B.G. Carranza Leon: None. K. Lytle: None. M.D. Jensen: None.