Inflammation plays a role in trans-10, cis-12 (10,12)-conjugated
linoleic acid (CLA)-mediated delipidation and
insulin resistance in adipocytes. Given the anti-inflammatory role of
resveratrol (RSV), we hypothesized that RSV would attenuate
inflammation and
insulin resistance caused by 10,12 CLA in human adipocytes. RSV blocked 10,12 CLA induction of the inflammatory response by preventing activation of extracellular signal-related
kinase and induction of inflammatory gene expression (i.e., IL-6, IL-8, IL-1beta) within 12 h. Similarly, RSV suppressed 10,12 CLA-mediated activation of the inflammatory
prostaglandin pathway involving
phospholipase A(2),
cyclooxygenase-2, and
PGF(2alpha). In addition, RSV attenuated 10,12 CLA increase of intracellular
calcium and
reactive oxygen species associated with cellular stress, and activation of stress-related
proteins (i.e.,
activating transcription factor 3, JNK) within 12 h. 10,12 CLA-mediated
insulin resistance and suppression of
fatty acid uptake and
triglyceride content were attenuated by RSV. Finally, 10,12 CLA-mediated decrease of
peroxisome proliferator-activated receptor gamma (
PPARgamma)
protein levels and activation of a peroxisome proliferator response element (PPRE) reporter were prevented by RSV. RSV increased the basal activity of PPRE, suggesting that RSV increases
PPARgamma activity. Collectively, these data demonstrate for the first time that RSV prevents 10,12 CLA-mediated
insulin resistance and delipidation in human adipocytes by attenuating
inflammation and cellular stress and increasing
PPARgamma activity.