HDAC9 in Insulin Resistance: An Update on Epigenetic Mechanisms, Inflammatory Crosstalk, and Therapeutic Potential.

Insulin resistance is one of the main causes of type 2 diabetes mellitus and metabolic disorders. Histone deacetylase 9 (HDAC9) belongs to the class IIa histone deacetylase family. It remodels chromatin structure and modulates gene expression to regulate adipocyte differentiation, inflammatory responses, and hepatic glucose homeostasis, thereby inhibiting insulin signaling. However, the complete and precise molecular mechanisms underlying these processes remain unclear. This review systematically summarizes the molecular characteristics and regulatory mechanisms of HDAC9, and analyzes its biological functions under insulin resistance from the perspectives of chromatin remodeling and transcriptional regulation. This review further explores whether HDAC9 exacerbates insulin resistance through regulating adipocyte differentiation, mediating inflammatory responses and disrupting hepatic glucose metabolic homeostasis. Meanwhile, this review evaluates HDAC9-targeted therapeutic prospects for metabolic diseases and offer theoretical support for future precision interventions.