Deficiency of IKKε inhibits inflammation and induces cardiac protection in high-fat diet-induced obesity in mice

Cao,Changchun; Li,Liangpeng; Chen,Wen; Zhu,Yifan; Qi,Yongchao; Wang,Xiaodi; Wan,Xin; Chen,Xin

doi:10.3892/ijmm.2014.1746

July-2014 Volume 34 Issue 1

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July-2014 Volume 34 Issue 1

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Article

Deficiency of IKKε inhibits inflammation and induces cardiac protection in high-fat diet-induced obesity in mice

Authors:
- Changchun Cao
- Liangpeng Li
- Wen Chen
- Yifan Zhu
- Yongchao Qi
- Xiaodi Wang
- Xin Wan
- Xin Chen
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Affiliations: Department of Nephrology, Nanjing Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China, Department of Thoracic and Cardiovascular Surgery, Nanjing Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China
Pages: 244-252
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Published online on: April 17, 2014

https://doi.org/10.3892/ijmm.2014.1746
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Abstract

Immune response and metabolic regulation have been recognized as a central homeostatic mechanism, the dysfunction of which can trigger a cluster of chronic metabolic disorders, particularly obesity, type Ⅱ diabetes and cardiovascular disease. Serine/threonine kinase IκB kinase (IKK) ε is a multifunctional regulator that participates in immune regulation, cell proliferation and transformation, and oncogenesis. In the present study, we investigated the role of IKKε in cardiovascular disorders using murine models of apolipoprotein E‑deficient [ApoE(-/-)] mice and ApoE/IKKε double‑knockout [ApoE(-/-)/IKKε(-/-)]mice, which were fed a normal diet (ND) and high-fat diet (HFD) for 12 weeks, respectively. Results of this study showed that mouse obesity correlated in vivo with an increased expression of IKKε. Additionally, chronic low‑grade inflammation in cardiac tissue was evident in ApoE(-/-) mice, but was markedly reduced in ApoE(-/-)/IKKε(-/-) mice. However, serum lipid levels in the ApoE(-/-) mice group were not significantly higher than those of the ApoE(-/-)/IKKε(-/-) group. Furthermore, immunofluorescence and western blot analysis demonstrated evident increases in the expression of nuclear factor-κB (NF-κB) pathway components and downstream factors in the ApoE(-/-) mice group, while these increases were blocked in the ApoE(-/-)/IKKε(-/-) group. Taken together, these data indicate that deficiency of IKKε prevented obesity and inflammatory response in the murine hearts in ApoE(-/-) and ApoE(-/-)/IKKε(-/-) mice fed an ND and HFD, respectively, suggesting that IKKε may play a role in HFD-induced inflammation in hearts of obese mice and may serve as a novel target for the treatment of a variety of metabolism-associated cardiovascular diseases.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Deficiency of IKKε inhibits inflammation and induces cardiac protection in high-fat diet-induced obesity in mice

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