Does Dietary Omega-6 Conjugated Linoleic Acid Isomers Battle or Boost Insulin Resistance and Vascular Diseases? Evidences and Molecular Insights.
Conjugated linoleic acid (CLA) refers to a group of positional and geometric isomers of conjugated dienoic-octadecadienoate (C18:2) that are abundant in dairy products and ruminant meat. Among all CLA isomers, cis-9, trans-11 (c9, t11) and trans-10, cis-12 (t10, c12) being the most abundant and studied. We recently demonstrated in L6 skeletal muscle cells that CLA isomers exhibit isomer-specific effects on glucose transport and GLUT4 trafficking. Of note, the potentiation of insulin-mediated glucose uptake and Akt phosphorylation by CLA isomers indicated that these isomers act via an insulin-independent, parallel glucose uptake pathway. Further cell signalling studies established a novel molecular mechanism involving Cai2+ release-CaMKIIα-AMPKα-AS160-GLUT4, by which t10,c12-CLA mediates skeletal muscle glucose uptake, whereas the mechanism of c9,t11-CLA remained unclear. These findings demonstrated that CLA isomers sensitise insulin action and possibly mimic properties of conventional PPAR agonists. Of note, unlike PPAR agonists, CLA has shown to prevent cardiac hypertrophy, improve blood pressure and decrease low density lipoprotein cholesterol. We thus hypothesised that CLA could either substitute or ameliorate adverse effects of PPAR agonists by distinct mechanisms. ApoE null mice fed with Western diet (WD) were administered 1:1 c9, t11 and t10, c12 CLA either from an early age or after 12 weeks by oral gavage. Select mice received intraperitoneal injections of either 0.6 mg/kg rosiglitazone or saline. The outcome and its interpretations to be deliberated. Nonetheless, the unique features of CLA isomers warrant extensive investigation to determine their potential clinical relevance for combating insulin resistance and vascular diseases.