Effects of trans ‐10, cis ‐12 and cis ‐9, trans ‐11 CLA on atherosclerosis in apoE/LDLR −/− mice

Abstract

The objective of our studies was to verify the potential health-related, anti-atherogenic potency of CLA isomers, fed to apolipoprotein E and LDL receptor double knockout mice (apoE/LDLR−/−), representing a reliable model of atherogenesis. Additionally, the effect of CLA isomers on liver steatosis was observed. In a “long experiment” (LONG), 2-month-old mice with no atherosclerosis were randomly assigned to three experimental groups and fed for the next 4 months. In a “short experiment” (SHORT), 4-month-old mice, with pre-established atherosclerosis, were randomly assigned to three experimental groups and fed for the next 2 months. The experimental diets were: AIN-93G (control), AIN-93G + 0.5% trans-10,cis-12 CLA (t10,c12), and AIN-93G + 0.5% cis9,trans-11 CLA (c9,t11). In both experiments, c9,t11 CLA increased mice body weight. In mice fed t10,c12 CLA weight of liver was threefold (p<0.05) increased what was linked with hepatic steatosis observed in LONG and SHORT experiment. In LONG experiment, t10,c12 CLA significantly (p<0.05) increased plasma TAGs, whereas no such effect was observed in SHORT one. In mice receiving the CLA isomers the level of PPARα and SREBP-1 mRNA in liver were significantly decreased. The expression of their target genes like ACO (PPARα) or FAS (SREBP-1) were not changed. Only c9,t11 increased ACO level in LONG experiment. There were no isomer-specific effects of CLA isomers on the area of atherosclerotic plaque. In conclusion, our results do not support the notion that CLA isomers supplementation to the diet has anti-atherosclerotic effects. CLA isomers have no effect on atherosclerosis in apoE/LDLR−/− mice. Practical applications: CLAs have been shown to occur naturally in food. In the last 10 years, attempts have been made to enrich animal-derived foods in CLA isomers through animal nutrition strategies. Indeed, these attempts resulted in production of functional food such as CLA-enriched milk (butter and cheese), ruminant and non-ruminant meat, as well as eggs. In addition to natural foodstuff, dietary CLA supplements can also contribute to CLA intake in humans. Commercial CLA preparations, fed to laboratory animals, showed several health-related properties, including anti-adipogenic, anti-carcinogenic, anti-atherogenic, and anti-inflammatory effects. The underlying mechanisms of action, however, are only poorly understood. The major objective of our studies was to verify the potential health-related, namely anti-atherogenic potency of CLA isomers, fed to apoE/LDLR−/− mice, representing unique and reliable model of atherogenesis. Additionally, effect of CLA isomers on steatosis was observed.