Pharmaceutical inhibition of IKKb/IKK2 protects the liver against NASH

Aims: NF-kB is inactive in the cytoplasm when bound to I-kB. Upon stimulation the IKK complex phosphorylates I-kB allowing NF-kB translocation to the nucleus initiating gene transcription. The IKK complex consists of two catalytic subunits (IKK1, IKK2) and a regulatory subunit (Nemo). IKK2 plays a key role in the development from steatosis to non-alcoholic steatohepatitis (NASH) by mediating insulin resistance. Hepatocyte specific IKK2 deletion improves glucose tolerance and myeloid cell specific IKK2 deletion ameliorates inflammation in dietary induced obesity. Aim: To investigate the effects of pharmaceutical…