Curcumin Improves Redox Status and Insulin Sensitivity in the Periphery and Decreases Leptin Receptor Expression in the Arcuate Nucleus in Obese Diabetic Mice.

Type 2 diabetes is characterized by chronic dysregulation of insulin signaling, leading to hyperglycemia, hyperinsulinemia, insulin resistance (IR), and obesity. Obesity is associated with alterations in appetite-regulating molecules such as leptin and its receptor, while oxidative stress contributes to disease progression. Curcumin (CUR), a natural antioxidant, may reduce oxidative damage and modulate the expression of molecules involved in appetite regulation and insulin sensitivity under diabetic-obese conditions. To evaluate this, 2-day-old male C57BL/6 mice were injected with streptozotocin (70 mg/kg), maintained on a high-fat diet for 8 weeks, and treated with CUR (50 mg/kg) for 4 weeks. Diabetic mice developed hyperglycemia, IR, and obesity, accompanied by decreased glutathione peroxidase activity in visceral (VAT) and brown (BAT) adipose tissues, as well as increased carbonylated protein (PCO) levels in BAT. Additionally, leptin levels were elevated in VAT and plasma, along with increased hypothalamic expression of the leptin receptor b isoform (Lep-Rb). CUR treatment improved peripheral insulin sensitivity and antioxidant activity, reduced PCO levels in BAT, and decreased hypothalamic Lep-Rb expression. These findings suggest that CUR improves insulin sensitivity and redox balance while reducing hypothalamic Lep-Rb expression, suggesting a potential role in restoring energy metabolism, glucose homeostasis, and appetite control in diabetic-obese mice.