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

: 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 cardio-vascular disease. Serine/threonine kinase IκB kinase (IKK) e is a multifunctional regulator that participates in immune regulation, cell proliferation and transformation, and oncogenesis. In the present study, we investigated the role of IKKe in cardiovascular disorders using murine models of apolipo-protein E‑deficient [ApoE(-/-)] mice and ApoE/IKKe double‑knockout [ApoE(-/-)/IKKe(-/-)]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 IKKe. Additionally, chronic low‑grade inflammation in cardiac tissue was evident in ApoE(-/-) mice, but was markedly reduced in ApoE(-/-)/IKKe(-/-) mice. However, serum lipid levels in the ApoE(-/-) mice group were not significantly higher than those of the ApoE(-/-)/IKKe(-/-) 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(-/-)/IKKe(-/-) group. Taken together, these data indicate that deficiency of IKKe prevented obesity and inflammatory response in the murine hearts in ApoE(-/-) and ApoE(-/-)/IKKe(-/-) mice fed an ND and HFD, respectively, suggesting that IKKe 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.