Adipsin deficiency does not impact atherosclerosis development in Ldlr-/- mice.

Obesity is a potent risk factor for atherosclerotic morbidity and mortality. Cytokines secreted from adipose tissue, namely, adipokines, have been suggested to be actively involved in atherosclerosis. One of the most abundant adipokines, adipsin, is downregulated in obesity. It catalyzes the rate-limiting step of alternative complement activation, which is one of the three complement pathways potentially involved in inflammation in atherosclerosis. Interestingly, adipsin has been identified as a novel biomarker in human coronary artery disease. However, its role in the development of atherosclerosis remains unexplored. We crossed adipsin-/- mice onto an Ldlr-/- background [double-knockout (DKO) mice] and induced atherogenesis by high-fat and high-cholesterol feeding. Metabolic profiles were systemically characterized, and atherosclerotic plaques were measured at both aortic root and arch regions. Western blotting was conducted to assess adipsin level and complement activity. The DKO mice exhibited similar sizes of atherosclerotic lesions as Ldlr-/- control mice at both the aortic root and arch regions. Accordingly, they displayed comparable metabolic parameters, including body weight, insulin sensitivity, and lipid profiles, along with compensated complement activity. Adipsin deficiency does not impact the development of atherosclerosis in Ldlr-/- mice despite its crucial function in alternative complement activation. Therefore, it is unlikely to play an important role in mediating the risk of atherosclerotic complications in obesity.NEW & NOTEWORTHY Adipsin deficiency does not impact the development of atherosclerosis in Ldlr-/- mice despite its crucial function in alternative complement activation. Therefore, it is unlikely to play an important role in mediating the risk of atherosclerotic complications in obesity.