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

J Am Heart Assoc. 2019 Jun 18;8(12):e012009. doi: 10.1161/JAHA.119.012009. Epub 2019 Jun 15.

Abstract

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 βΔAd 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 βΔAd 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 βΔAd 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.

Keywords: adipocyte; arteriosclerosis; inflammation; nuclear factor‐κB.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptor Proteins, Signal Transducing / deficiency*
  • Adipocytes / enzymology*
  • Animals
  • I-kappa B Kinase / deficiency*
  • Male
  • Mice, Obese
  • Plaque, Atherosclerotic / etiology*

Substances

  • Adaptor Proteins, Signal Transducing
  • Ldlrap1 protein, mouse
  • I-kappa B Kinase