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). Here, INS is linked to metabolic syndrome.