Here, we investigated myeloid HDAC7 functions in obesity-driven metabolic disease.<h4>Methods</h4>We used gain- and loss-of-function genetic approaches in mice to investigate myeloid HDAC7 functions in hepatic inflammation and metabolic disease, as well as associations with hepatic gene signatures characteristic of advanced chronic liver disease (CLD).<h4>Results</h4>Transgenic expression of <i>Hdac7</i> in myeloid cells increased liver inflammation and liver mRNA levels of <i>Ccl2</i> and <i>Il1b</i>, key inflammatory mediators linked to CLD. The gene discussed is CCL2; the disease is obesity due to melanocortin 4 receptor deficiency.