CNR1 and metabolic syndrome: Indeed, genetic deletion of CB1R in hepatocytes partially protects mice from developing DIO-related hepatic steatosis, hyperglycemia, dyslipidemia, and insulin resistance (Osei-Hyiaman et al., 2008), whereas its overexpression in hepatocytes contributes to insulin resistance via inhibition of insulin signaling and clearance (Liu et al., 2012).