Resveratrol Attenuates Conjugated Linoleic Acid (CLA)‐Mediated Inflammation, Endoplasmic Reticulum (ER) Stress, and Delipidation of Human Adipocytes

Abstract

Inflammation and ER stress have been shown to play a role in trans‐10, cis‐12 CLA (10,12 CLA)‐mediated delipidation and insulin resistance in adipocytes. We hypothesized that resveratrol (RSV), an anti‐inflammatory polyphenol, would attenuate inflammation, ER stress, and delipidation caused by 10,12 CLA. Primary cultures of human adipocytes were treated with 10,12 CLA in the absence or presence of RSV acutely (6–48 h) and chronically (7 d). RSV blocked 10,12 CLA induction of inflammatory gene expression (IL‐6, IL‐8, IL‐1B) and activation of extracellular signal related kinase (ERK) within 12 h. Consistent with these data, RSV suppressed 10,12 CLA activation of the inflammatory prostaglandin (PG) pathway involving phospholipase A2, cyclooxygenase‐2 (COX‐2), and PGF2a. RSV attenuated 10,12 CLA increase of intracellular calcium, induction of ER‐stress related genes (ATF3, GADD34), and proteins (ATF3, JNK). 10,12 CLA suppression of a PPARg reporter was attenuated by RSV. Consistent with these findings, RSV attenuated 10,12 CLA suppression of adipogenic/lipogenic genes (adiponectin, aP2, GLUT4, SCD1, ACC). Lastly, insulin resistance and delipidation by 10,12 CLA were attenuated by RSV. Collectively, these data suggest that RSV prevents 10,12 CLA‐mediated delipidation in human adipocytes through suppression of inflammation and ER stress. Supported by 2R01‐DK063070, F31DK076208, and NCARS 06771.