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 IKK β (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 IKK β signaling in adipocytes can also affect atherogenesis. This study aims to investigate the impact of adipocyte IKK β 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 IKK β in atherogenesis, we generated adipocyte-specific IKK β-deficient LDLR ^-/- ( IKK β^ΔAd LDLR ^-/-) mice. Targeted deletion of IKK β 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, IKK β^ΔAd LDLR ^-/- mice had defective adipose remodeling and increased adipose tissue and systemic inflammation. Deficiency of adipocyte IKK β did not affect atherosclerotic lesion sizes but resulted in enhanced lesional inflammation and increased plaque vulnerability in obese IKK β^ΔAd LDLR ^-/- mice. Conclusions These data demonstrate that adipocyte IKK β signaling affects the evolution of atherosclerosis plaque vulnerability in obese LDLR ^-/- mice. This study suggests that the functions of IKK β signaling in atherogenesis are complex, and IKK β in different cell types or tissues may have different effects on atherosclerosis development.