Omentin attenuates atherosclerotic lesion formation in apolipoprotein E-deficient mice.

Abstract

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.

• Authors: Mizuho Hiramatsu-Ito, Rei Shibata, Koji Ohashi, Yusuke Uemura, Noriyoshi Kanemura, Takahiro Kambara, Takashi Enomoto, Daisuke Yuasa, Kazuhiro Matsuo, Masanori Ito, Satoko Hayakawa, Hayato Ogawa, Naoya Otaka, Shinji Kihara, Toyoaki Murohara, Noriyuki Ouchi
• Journal: Cardiovascular research (Cardiovasc Res) Vol. 110 Issue 1 Pg. 107-17 (May 01 2016) ISSN: 1755-3245 [Electronic] England
• PMID: 26714927 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: [email protected].

Chemical References

• Apolipoproteins E
• Cytokines
• GPI-Linked Proteins
• ITLN1 protein, human
• Interleukin-6
• Itln1 protein, mouse
• Lectins
• Tumor Necrosis Factor-alpha

Topics

• Animals
• Apolipoproteins E (deficiency, metabolism)
• Atherosclerosis (genetics, metabolism)
• Cells, Cultured
• Cytokines (metabolism)
• Disease Models, Animal
• GPI-Linked Proteins (metabolism)
• Humans
• Interleukin-6 (metabolism)
• Lectins (metabolism)
• Macrophages (metabolism)
• Mice, Inbred C57BL
• Mice, Transgenic
• Tumor Necrosis Factor-alpha (metabolism)