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

TitleInterleukin-1β and prostaglandin-synthesizing enzymes as modulators of human omental and subcutaneous adipose tissue function.
Publication TypeJournal Article
Year of Publication2019
AuteursLabrecque, J, Michaud, A, Gauthier, M-F, Pelletier, M, Julien, F, Bouvet-Bouchard, L, Tchernof, A
JournalProstaglandins Leukot Essent Fatty Acids
Date Published2019 02
KeywordsAdipocytes, Adipogenesis, Aldehyde Reductase, Cell Differentiation, Cyclooxygenase 2, Cyclooxygenase 2 Inhibitors, Cytokines, Dinoprost, Dinoprostone, Female, Humans, Inflammation, Interleukin-1beta, Intra-Abdominal Fat, Male, Middle Aged, Nitrobenzenes, Obesity, Omentum, Phthalazines, PPAR gamma, Subcutaneous Fat, Abdominal, Sulfonamides

IL-1β 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-1β, 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-1β 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-1β. Preadipocyte differentiation experiments were also performed. IL-1β 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-1β blunted PGF and PGE release, but did not alter IL-1β effects on adipose tissue function markers. IL-1β down-regulated adipocyte differentiation whereas NS-398 alone increased this process. However, NS-398 did not prevent IL-1β inhibition of adipogenesis. We conclude that IL-1β induces a pro-inflammatory response in human adipose tissues, particularly in visceral fat, and acts independently of concomitant PG release. IL-1β and COX-2 appear to be critical determinants of adipose tissue pathophysiologic remodeling in obesity.

Alternate JournalProstaglandins Leukot. Essent. Fatty Acids
PubMed ID30661603
Grant List / / CIHR / Canada