Interleukin-1ß and prostaglandin-synthesizing enzymes as modulators of human omental and subcutaneous adipose tissue function.

IL-1ß stimulates expression of prostaglandin (PG)-synthesizing enzymes cyclooxygenase (COX)-2 and aldo-keto reductase (AKR)1B1 in human preadipocytes. We aimed to examine the impact of IL-1ß, COX-2 and AKR1B1 on markers of human visceral and subcutaneous adipose tissue function, and to assess whether PG synthesis by these enzymes mediates IL-1ß effects. Omental and subcutaneous fat samples were obtained from bariatric surgery patients. PG release and expression of inflammatory and adipogenic markers were assessed in explants treated with COX-2 inhibitor NS-398 or AKR1B1 inhibitor Statil, with or without IL-1ß. Preadipocyte differentiation experiments were also performed. IL-1ß decreased expression of PPARγ in both fat depots compared to control and increased expression of NF-κB1, IL-6, CCL-5, ICAM-1 and VEGFA, especially in visceral fat for IL-6, CCL-5 and VEGFA. Adding Statil or NS-398 to IL-1ß blunted PGF2α and PGE2 release, but did not alter IL-1ß effects on adipose tissue function markers. IL-1ß down-regulated adipocyte differentiation whereas NS-398 alone increased this process. However, NS-398 did not prevent IL-1ß inhibition of adipogenesis. We conclude that IL-1ß induces a pro-inflammatory response in human adipose tissues, particularly in visceral fat, and acts independently of concomitant PG release. IL-1ß and COX-2 appear to be critical determinants of adipose tissue pathophysiologic remodeling in obesity.