HDAC8 is activated by SREBP-1, an insulin-responsive TF which increases the transcription of lipogenic genes, and HDAC8 knockdown in obesity-promoted mouse models of NASH and HCC attenuated IR, reduced triglyceride levels and reduced tumour growth, potentially through widespread changes in TGFβ and mitogen-activated protein kinase/c-Jun N-terminal kinase (MAPK/JNK) signalling (107). Here, HDAC8 is linked to obesity due to melanocortin 4 receptor deficiency.