Changcheng Zhou
University of Kentucky, USA
Title: Targeting IKKβ signaling for treatment of Obesity and Diabetes
Biography
Biography: Changcheng Zhou
Abstract
Obesity is associated with a state of chronic low-grade inflammation that is a major contributor to insulin resistance and diabetes. IκB kinase β (IKKβ), a central coordinator of inflammation through activation of NF-κB, has been implicated in the pathogenesis of obesity-associated metabolic disorders. However, the role of IKKβ in adipose tissue development and metabolism remains elusive. We have recently revealed an important role of IKKβ in the regulation of adipocyte differentiation and adipose tissue development in response to high-fat feeding. Deficiency of IKKβ in adipocyte precursor cells diminished the ability of these cells to differentiate into adipocytes. By analyzing mice that selectively lack IKKβ in the white adipose lineage, we found that deficiency of IKKβ protected mice from high-fat diet-induced obesity. Moreover, IKKβ deficient mice had decreased plasma proinflammatory cytokine levels and enhanced insulin sensitivity. Pharmacological inhibition of IKKβ also efficiently inhibited both murine and human adipocyte differentiation. Further, chronic treatment of mice with a potent IKKβ inhibitor ameliorated diet-induced obesity and insulin resistance. Our findings demonstrate a pivotal role of IKKβ in linking overnutrition to adipose tissue development and insulin resistance, and provide strong evidence for using appropriate IKKβ inhibitors in the treatment of obesity and metabolic disorders.
