Adipocytes take up glucose in response to insulin via the GLUT4 glucose transporter. Glucose-dependent lipid synthesis and histone acetylation are ACLY-dependent, and GLUT4 expression is regulated in an ACLY-dependent manner in adipocytes[16,22,25]. Both adipocyte de novo lipogenesis and adipocyte GLUT4 expression are associated with improved systemic insulin sensitivity [35,36,38]. Since ACLY levels in adipocytes are suppressed by high fat feeding and obesity [25], it is plausible that low ACLY levels contribute to development of insulin resistance via ACLY’s dual roles in gene regulation and lipid synthesis.