Translational Medical Research Commons^™

Targeting Iκb Kinase Β In Adipocyte Lineage Cells For Treatment Of Obesity And Metabolic Dysfunctions, Robert N. Helsley, Yipeng Sui, Se-Hyung Park, Zun Liu, Richard G. Lee, Beibei Zhu, Philip A. Kern, Changcheng Zhou

Clinical and Translational Science Faculty Publications

IκB kinase β (IKKβ), a central coordinator of inflammation through activation of nuclear factor-κB, has been identified as a potential therapeutic target for the treatment of obesity-associated metabolic dysfunctions. In this study, we evaluated an antisense oligonucleotide (ASO) inhibitor of IKKβ and found that IKKβ ASO ameliorated diet-induced metabolic dysfunctions in mice. Interestingly, IKKβ ASO also inhibited adipocyte differentiation and reduced adiposity in high-fat (HF)-fed mice, indicating an important role of IKKβ signaling in the regulation of adipocyte differentiation. Indeed, CRISPR/Cas9-mediated genomic deletion of IKKβ in 3T3-L1 preadipocytes blocked these cells differentiating into adipocytes. To further elucidate the role of …