While it has been suggested that mixed CLA supplementation may have anti-atherogenic properties in certain mouse models [8,9,10,11,12,30], we now show for the first time that obese HFHS diet-fed Ldlr−/− mice, which represent a more humanized model of metabolic syndrome, are protected from atherosclerosis following CLA supplementation, and that the 10,12 isomer of CLA is responsible for this protection. Here, LDLR is linked to atherosclerosis.