Adipose Tissue Inflammation is Not Related to Adipose Insulin Resistance in Humans

The role of adipose tissue (AT) inflammation on AT function in humans is unclear. We tested whether AT macrophage (ATM) content, cytokine gene expression and senescent cell burden (markers of AT inflammation) predict AT insulin resistance measured as the insulin concentration that suppresses lipolysis by 50% (IC₅₀). We studied 86 volunteers with normal weight or obesity at baseline, and a subgroup of 25 volunteers with obesity before and after weight loss. There was a strong, positive relationship between IC₅₀ and abdominal subcutaneous and femoral fat cell size (FCS). The positive, univariate relationships between IC₅₀ and abdominal AT inflammatory markers: CD68, CD14, CD206 ATM/100 adipocytes, senescent cells, IL-6 and TNF-α mRNA were not significant after adjustment for FCS. A 10% weight loss significantly reduced IC₅₀, however, there was no reduction in adipose ATM content, senescent cells or cytokine gene expression. Our study suggests that commonly used markers of AT inflammation are not causally linked to AT insulin resistance, whereas FCS is a strong predictor of AT insulin resistance with respect to lipolysis.