The weight loss supplement conjugated linoleic acid (CLA) consists of an equal mixture of trans-10, cis-12 (10,12) and cis-9, trans-11 (9,11) isomers. However, high levels of mixed CLA isomers, or the 10,12 isomer, causes chronic inflammation, lipodystrophy, or insulin resistance. We previously demonstrated that 10,12 CLA decreases de novo lipid synthesis along with the abundance and activity of stearoyl-CoA desaturase (SCD)-1, a delta-9 desaturase essential for the synthesis of monounsaturated fatty acids (MUFA). Thus, we hypothesized that the 10,12 CLA-mediated decrease in SCD-1, with the subsequent decrease in MUFA, was responsible for the observed effects. To test this hypothesis, 10,12 CLA-treated human adipocytes were supplemented with oleic acid for 12 h to 7 d, and inflammatory gene expression, insulin-stimulated glucose uptake, and lipid content were measured. Oleic acid reduced inflammatory gene expression in a dose-dependent manner, and restored the lipid content of 10,12 CLA-treated adipocytes without improving insulin-stimulated glucose uptake. In contrast, supplementation with stearic acid, a substrate for SCD-1, or 9,11 CLA did not prevent inflammatory gene expression by 10,12 CLA. Notably, 10,12 CLA impacted the expression of several G-protein coupled receptors that was attenuated by oleic acid. Collectively, these data show that oleic acid attenuates 10,12 CLA-induced inflammatory gene expression and lipid content, possibly by alleviating cell stress caused by the inhibition of MUFA needed for phospholipid and neutral lipid synthesis.

CLA is a popular weight loss supplement consisting of 10,12 and cis‐9, trans‐11 (9,11) isomers that reduces adiposity. However, the consumption of CLA, particularly the 10,12 isomer, is associated with adverse side effects including chronic inflammation and insulin resistance. We hypothesized that these side effects of 10,12 CLA were linked to reduced activity of lipogenic enzymes including stearoyl‐CoA desaturase (SCD)‐1, a delta‐9 desaturase essential for the production of monounsaturated fatty acid (MUFA)s that are required for phospholipid and neutral lipid synthesis. Furthermore, blocking SCD‐1 increases saturated fatty acids like palmitate and stearate, which increase inflammation and insulin resistance. Thus, cultures of human adipocytes were treated with 50 uM 10,12 CLA and 30–300 uM oleic acid for 18–48 h. Consistent with our hypothesis, oleic acid reduced CLA‐mediated inflammatory gene expression in a dose‐dependent manner. However, oleic acid treatment did not attenuate CLA‐mediated insulin resistance. Notably, supplementation with stearic acid, a substrate for SCD‐1, or 9,11 CLA did not prevent inflammatory gene expression in 10,12 CLA‐treated cultures. Collectively, these data show that oleic acid attenuates CLA‐mediated inflammatory signaling, possibly by alleviating stress caused by SCD‐1 inhibition. Supported by NIH NIDDK‐ODS 5R01 DK063070‐09 and the UNCG URA program.