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Conjugated Linoleic Acids (CLA) and Insulin Resistance: Differential Effects of CLA Isomers on Endoplasmic Reticulum (ER) Stress
Author(s) -
Dammanahalli Jagadeesha K,
Subbaiah Papasani V
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.851.7
Subject(s) - endoplasmic reticulum , conjugated linoleic acid , unfolded protein response , insulin resistance , linoleic acid , chemistry , adipocyte , biochemistry , biology , insulin , adipose tissue , endocrinology , medicine , fatty acid
Conjugated linoleic acids (CLA), the naturally occurring fatty acids prevalent in dairy products, are being used by the general public for potential health benefits, including weight loss, and cancer prevention, but they have also been reported to cause insulin resistance (IR) in animal models. However, the mechanism of action of CLA is not well understood. The current study tested the hypothesis that the development of insulin resistance after consumption of specific CLA isomers is due to the induction of endoplasmic reticulum (ER) stress. We tested the effects of four different CLA isomers, trans ‐10, cis ‐12 (t10c12)‐, cis 9, trans 11 (c9t11), trans 9 trans 11 (t9t11) and cis 9 cis 11 (c9c11) in three different cell lines‐ HepG2 (hepatocyte), c2c12 (myocyte) and 3T3‐L1 (adipocyte). The cells were treated with 0–100 μM CLA for 24 h, and analyzed for reactive oxygen species (ROS) by flow cytometry, and for ER stress markers by Western blotting. We found that both t9t11, and t10c12‐CLAs induced ROS and the expression of GRP78, the central regulator of ER stress, at 50 μM concentration in HePG2 and 3T3 cells. However these effects were elicited only by the t9t11 isomer in c2c12 cells. GADD153 (CHOP), another marker of ER stress, was induced by t10c12 in HepG2 and 3T3 cells whereas, c9t11, t9t11 and c9c11‐CLAs induced it in 3T3 and c2c12 cells but not in HepG2 cells. Further studies demonstrated that the t10c12 isomer inhibited the insulin‐stimulated phosphorylation of insulin receptor and AKT in HepG2 cells, whereas the c9t11, c9c11 and t9t11 isomers increased the phosphorylation of both proteins. These findings suggest that t10 c12 CLA, the isomer known to cause insulin resistance in mice, may do so by inducing ER stress. Support or Funding Information Supported by VA Merit Review BX001090