The liver responds to glucagon and insulin to regulate blood glucose levels through glycogen synthesis, glycogenolysis, and gluconeogenesis.2 However, in obesity and type 2 diabetes, these regulatory pathways are dysregulated, leading to excessive hepatic gluconeogenesis, elevated fasting blood glucose, increased lipid synthesis, and metabolic disorders such as hyperglycemia, hyperlipidemia, and MAFLD.2 Deciphering the mechanisms of hepatic metabolic dysregulation is important for the treatment of obesity, type 2 diabetes, and MAFLD. The gene discussed is INS; the disease is obesity due to melanocortin 4 receptor deficiency.