Abstract 11475: Overexpression of Human Omentin in a Fat-Specific Manner Attenuates Atherosclerotic Lesion Formation in ApoE-Deficient Mice
Background: Obesity is closely associated with the progression of atherosclerosis. Omentin is a circulating adipokine, which is downregulated by obesity. Recently, we have shown that omentin concentrations are decreased in association with carotid atherosclerosis and coronary artery disease. Here, we investigated the impact of omentin on the development of atherosclerosis in vivo, and assessed its potential mechanisms.
Methods and Results: We generated transgenic mice expressing the human omentin gene under the control of the aP2 promoter (fat-specific OMT-Tg mice) in the background of C57BL/6J. Morphometric and metabolic parameters of OMT-Tg mice were indistinguishable from nontransgenic littermates under basal/physiological conditions. We also crossed OMT-Tg mice with apolipoprotein E-deficient (apoE-KO) mice, which are experimental models of atherosclerosis. Circulating levels of human omentin in apoE-KO/OMT-Tg mice were approximately 2.0 fold higher than in those in healthy human subjects, whereas human omentin protein was undetectable in apoE-KO mice. At the age of 20 weeks, apoE-KO/OMT-Tg mice exhibited a significant reduction of the atherosclerotic lesion area in the aortic sinus compared with apoE-KO mice. No significant difference was observed in glucose and lipid levels between two strains of mice. ApoE-KO/OMT-Tg mice also displayed a significant decrease in mRNA expression of inflammation-related genes including TNF-α, IL-6, MCP-1, and VCAM-1 in the aortic arch compared with apoE-KO mice. In cultured human monocyte-derived macrophages, treatment with a physiological concentration of recombinant human omentin protein significantly reduced cholesteryl ester content and lipid droplet formation. Omentin treatment also suppressed LPS-stimulated expression of TNF-α and IL-6 in human macrophages.
Conclusions: These data suggest that omentin derived from adipose tissue suppresses the development of atherosclerosis by reducing inflammatory responses of macrophage.
Author Disclosures: M. Hiramatsu-Ito: None. R. Shibata: None. K. Ohashi: None. T. Kambara: None. D. Yuasa: None. Y. Joki: None. S. Hayakawa: None. H. Ogawa: None. T. Murohara: None. N. Ouchi: None.
- © 2014 by American Heart Association, Inc.