Role of IKKε in the Metabolic Diseases: Physiology, Pathophysiology, and Pharmacology

  • Front Pharmacol. 2022 May 19:13:888588. doi: 10.3389/fphar.2022.888588.
Qing-Ao Xiao  1  2 ,  Qian He  1  3 ,  Lun Li  4  5 ,  Yinhong Song  4  5 ,  Yue-Ran Chen  2  6 ,  Jun Zeng  1 ,  Xuan Xia  2  6
Affiliations
  • 1. Department of Endocrinology, The People's Hospital of China Three Gorges University/the First People's Hospital of Yichang, Yichang, China.
  • 2. Third-grade Pharmacological Laboratory on Traditional Chinese MedicineState Administration of Traditional Chinese Medicine, China Three Gorges University, Yichang, China.
  • 3. National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China.
  • 4. The Institute of Infection and Inflammation, China Three Gorges University, Yichang, China.
  • 5. Department of Microbiology and Immunology, Medical College, China Three Gorges University, Yichang, China.
  • 6. Department of Physiology and Pathophysiology, Medical College, China Three Gorges University, Yichang, China.
PMID: 35662709 DOI: 10.3389/fphar.2022.888588
Abstract

IKKε (inhibitor of nuclear factor kappa-B kinase ε) is a member of the noncanonical NF-κB pathway. It participates in the inflammatory response and innate immunity against bacteria. In recent decades, IKKε has been closely associated with metabolic regulation. Inhibition of the IKKε pathway can improve fat deposition in the liver, reduce subcutaneous fat inflammation, and improve liver gluconeogenesis in obesity. IKKε is expected to be a new therapeutic target for metabolic diseases such as nonalcoholic fatty liver disease, diabetes, and obesity. Herein, we summarize the structural characterization, physiological function, and pathological role of IKKε in metabolic diseases and small molecule inhibitors of IKKε.

Keywords
amlexanox; diabetes; inhibitor of nuclear factor kappa-B kinase ε; metabolic diseases; nonalcoholic fatty liver disease; obesity.