Lack of association between adiponectin levels and atherosclerosis in mice.

OBJECTIVE:Adiponectin is an adipocyte-derived, secreted protein that is implicated in protection against a cluster of related metabolic disorders. Mice lacking adiponectin display impaired hepatic insulin sensitivity and respond only partially to peroxisome proliferator-activated receptor gamma agonists. Adiponectin has been associated with antiinflammatory and antiatherogenic properties; however, the direct involvement of adiponectin on the atherogenic process has not been studied. METHODS AND RESULTS:We crossed adiponectin knockout mice (Adn(-/-)) or mice with chronically elevated adiponectin levels (Adn(Tg)) into the low-density lipoprotein receptor-null (Ldlr(-/-)) and the apoliprotein E-null (Apoe(-/-)) mouse models. Adiponectin levels did not correlate with a suppression of the atherogenic process. Plaque volume in the aortic root, cholesterol accumulation in the aorta, and plaque morphology under various dietary conditions were not affected by circulating adiponectin levels. In light of the strong associations reported for adiponectin with cardiovascular disease in humans, the lack of a phenotype in gain- and loss-of-function studies in mice suggests a lack of causation for adiponectin in inhibiting the buildup of atherosclerotic lesions. CONCLUSIONS:These data indicate that the actions of adiponectin on the cardiovascular system are complex and multifaceted, with a minimal direct impact on atherosclerotic plaque formation in preclinical rodent models.