Involvement of cyclooxygenase-2 in synergistic effect of cyclic stretching and eicosapentaenoic acid on adipocyte differentiation.

The present study examined the combined effects of fish-oil-derived omega-3 polyunsaturated fatty acids, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and cyclic stretching on the adipocyte differentiation of 3T3-L1 cells. Treatment with EPA alone did not inhibit the differentiation, although it partially suppressed the expressions of peroxisome proliferator-activated receptor (PPAR)-gamma(2) and CCAAT/enhancer-binding protein (C/EBP)alpha transcripts, which are considered to be indispensable for the determination of adipocyte differentiation. However, the differentiation was significantly reduced when EPA but not DHA was concomitantly applied with cyclic stretching. In addition, EPA, but not DHA, could be a substrate of cyclooxygenase (COX)-2, and we found that the stretching significantly augmented the expression of COX-2 and that a selective COX-2 inhibitor (NS-398) inhibited the combined effect of the stretching and EPA. Taken together, it appears that the stretching and EPA exhibit a synergistic effect for the inhibition of adipocyte differentiation through stretch-induced COX-2.