Cyclooxygenase‐2 Induction by trans‐10, cis‐12 Conjugated Linoleic Acid in Adipose Tissue

Abstract

trans‐10, cis‐12 conjugated linoleic acid (10e12z) is the isomer linked with weight loss in animal and decreased adipose differentiation in cell culture models. The mechanism of this is still being determined. However, 10e12z induces an inflammatory response in adipose in the form of induction of interleukin (IL)‐6 and activation of NF‐κB. COX‐2 is an inflammatory mediator and is induced in response to NF‐κB. Therefore, we asked if there is a role for COX‐2 in the response of adipocytes to 10e12z. Here we show, in differentiating 3T3‐L1 cells, 10e12z reduces the ability of preadipocytes to differentiate and accumulate lipid, as measured by expression of markers such as aP2, C/EBPα and ADRP as well as oil red‐o staining. Furthermore, these effects of 10e12z are evident 5 days after induction of differentiation. Concurrently, a marked increase in the expression of COX‐2 by 10e12z treatment occurs before increases in IL‐6 expression. These results suggest that COX‐2 induction is adipocyte specific. Consistent with this, we could not induce COX‐2 in 3T3‐L1 preadipocytes. However, COX‐2 mRNA is induced rapidly in mature adipocytes reaching a maximum after 12 hours and declining to baseline after 48 hours. COX‐2 mRNA is also dose responsive, and can be significantly induced with 12.5 uM 10e12z CLA. These studies indicate that the induction of COX‐2 is an important event mediating the metabolic effects of 10e12z in adipocytes.