Mechanism Research of Reducing Obesity-Induced Insulin Resistance in the White Adipose Tissue by Knockdown of Neuropeptide Y Expression in the Dorsomedial Hypothalamus

This study investigated the specific mechanism of knockdown of neuropeptide Y (NPY) in reducing obesity-induced insulin resistance in the white adipose tissue. Adeno-associated virus (AAV)-mediated RNAi was utilized to downregulate NPY expression in rats fed either regular chow or high fat diet. By investigating the differences in rat body weight and food intake, we assessed the effect of knockdown of NPY expression on insulin sensitivity and β-cell proliferation. Glucose consumption and 2-[3H]DG uptake in 3T3-L1 adipocytes were assessed to determine the molecular mechanisms. The results showed that knockdown of NPY expression in the dorsomedial hypothalamus (DMH) reduced obesityinduced insulin resistance, increased glucose consumption, and decreased 2-[3H]DG uptake in 3T3-L1 adipocytes via the PI3K/Akt/GSK-3β signaling pathways and the NPY Y5 receptor.