Fig. 2. The effects of histone deacetylase 9 (HDAC9) on the development of chronic diseases in bone, adipose tissue, heart, and liver. HDAC9 facilitates osteoblast activity while inhibiting osteoclast differentiation, which may explain the protective effects of HDAC9 against osteoporosis in mice. Adipogenic differentiation of pre-adipocytes may help to alleviate hypoxia and dysfunctions of hypertrophied adipose tissue, which is inhibited by HDAC9. Also, mice with the deletion of Hdac9 are protected from diet-induced adipose tissue dysfunctions and systemic insulin resistance. Hdac9 deficiency also enhances cholesterol efflux from macrophages while inhibiting oxidized low-density lipoprotein-induced human endothelial cell apoptosis, indicating HDAC9 may exacerbate cardiovascular disease (CVD) development. Moreover, HDAC9 may contribute to hepatocellular carcinoma (HCC) development by suppressing miR-376a expression, a microRNA that induces the apoptosis of hepatocellular carcinoma cells. HDAC9 is also critical for hepatic stellate cell (HSC) activation and forkhead box O 1 (FOXO1)-dependent gluconeogenesis in the liver. Therefore, it may also be involved in the development of fibrosis and obesity-induced insulin resistance in the liver.