Deficiency of Adipocyte IKKβ Affects Atherosclerotic Plaque Vulnerability in Obese LDLR Deficient Mice

BACKGROUND: Obesity‐associated chronic inflammation has been known to contribute to atherosclerosis development, but the underlying mechanisms remain elusive. Recent studies have revealed novel functions of IKKβ (inhibitor of NF‐κB [nuclear factor κB] kinase β), a key coordinator of inflammation through activation of NF‐κB, in atherosclerosis and adipose tissue development. However, it is not clear whether IKKβ signaling in adipocytes can also affect atherogenesis. This study aims to investigate the impact of adipocyte IKKβ expression on atherosclerosis development in lean and obese LDLR (low‐density lipoprotein receptor)–deficient (LDLR (−/−)) mice. METHODS AND RESULTS: To define the role of adipocyte IKKβ in atherogenesis, we generated adipocyte‐specific IKKβ‐deficient LDLR (−/−) (IKKβ(ΔAd) LDLR (−/−)) mice. Targeted deletion of IKKβ in adipocytes did not affect adiposity and atherosclerosis in lean LDLR (−/−) mice when fed a low‐fat diet. In response to high‐fat feeding, however, IKKβ(ΔAd) LDLR (−/−) mice had defective adipose remodeling and increased adipose tissue and systemic inflammation. Deficiency of adipocyte IKKβ did not affect atherosclerotic lesion sizes but resulted in enhanced lesional inflammation and increased plaque vulnerability in obese IKKβ(ΔAd) LDLR (−/−) mice. CONCLUSIONS: These data demonstrate that adipocyte IKKβ signaling affects the evolution of atherosclerosis plaque vulnerability in obese LDLR (−/−) mice. This study suggests that the functions of IKKβ signaling in atherogenesis are complex, and IKKβ in different cell types or tissues may have different effects on atherosclerosis development.