Omentin attenuates atherosclerotic lesion formation in apolipoprotein E-deficient mice
| Autor: | Noriyuki Ouchi, Takahiro Kambara, Hayato Ogawa, Naoya Otaka, Satoko Hayakawa, Koji Ohashi, Masanori Ito, Rei Shibata, Shinji Kihara, Toyoaki Murohara, Kazuhiro Matsuo, Takashi Enomoto, Mizuho Hiramatsu-Ito, Yusuke Uemura, Daisuke Yuasa, Noriyoshi Kanemura |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Apolipoprotein E medicine.medical_specialty Apolipoprotein B biology Physiology Monocyte 030204 cardiovascular system & hematology Proinflammatory cytokine 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine Endocrinology medicine.anatomical_structure chemistry Physiology (medical) Internal medicine biology.protein medicine Cholesteryl ester Tumor necrosis factor alpha Cardiology and Cardiovascular Medicine Interleukin 6 Protein kinase B |
| Zdroj: | Cardiovascular Research. 110:107-117 |
| ISSN: | 1755-3245 0008-6363 |
| DOI: | 10.1093/cvr/cvv282 |
| Popis: | Aims Obesity is associated with the development of atherosclerosis. We previously demonstrated that omentin is a circulating adipokine that is downregulated in association with atherosclerotic diseases. Here, we examined the impact of omentin on the development of atherosclerosis with gain-of-function genetic manipulations and dissected its potential mechanism. Methods and results Apolipoprotein E-deficient (apoE-KO) mice were crossed with transgenic mice expressing the human omentin gene (OMT-Tg) mice in fat tissue to generate apoE-KO/OMT-Tg mice. ApoE-KO/OMT-Tg mice exhibited a significant reduction of the atherosclerotic areas in aortic sinus, compared with apoE-KO mice despite similar lipid levels. ApoE-KO/OMT-Tg mice also displayed significant decreases in macrophage accumulation and mRNA expression of proinflammatory mediators including tumour necrosis factor-α, interleukin-6, and monocyte chemotactic protein-1 in aorta when compared with apoE-KO mice. Treatment of human monocyte-derived macrophages with a physiological concentration of human omentin protein led to reduction of lipid droplets and cholesteryl ester content. Treatment with human omentin protein also reduced lipopolysaccharide-induced expression of proinflammatory genes in human macrophages. Treatment of human macrophages with omentin promoted the phosphorylation of Akt. Inhibition of Akt signalling abolished the anti-inflammatory actions of omentin in macrophages. Conclusion These data document for the first time that omentin reduces the development of atherosclerosis by reducing inflammatory response of macrophages through the Akt-dependent mechanisms. |
| Databáze: | OpenAIRE |
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