The Role of β3-adrenergic Receptor Gene in Neuropeptide Y Y5Receptor Antisense Gene Therapy of Diet-induced Obese Rats

Objective: To study the role of 3-adreneric receptor gene in neuropeptide Y(NPY) Y5 receptor antisense gene therapy of diet-induced obese rats. Methods: The diet-induced obese rats were prepared by feeding a high-nutrition diet. Lateral ventricular was cannulated in obese rats which then received an intraventricular injection of either 5µg/µl NPY Y5 receptor anti- sense or 10µl missense oligodeoxynucleotide or saline of 10µl respectively in every rat. When the rats were killed, the wet weight of abdominal adipose tissue, the level of serum lipid and lipoprotein were measured. Total RNA from the retroperitoneal adipose tissue was extracted and the level of β3-adrenergic receptor gene mRNA expression was evaluated by RT-PCR. Results: ① The wet weight of abdominal adipose tissue, the levels of serum lipids were greatly higher in diet-induced obese rats than those in normal rats. However, there were much lower β3-adrenergic receptor gene mRNA expression levels in retroperitoneal adipose tissue in diet-induced obese rats as compared with those in normal rats. ② After the diet-induced obese rats were intraventricularly administered with NPY Y5 receptor antisense oligodeoxynucleotide, the levels of β3-adrenergic receptor gene mRNA expression in retroperitoneal adipose tissue of diet-induced obese rats were strikingly up-regulated, whereas the wet weight of abdominal adipose tissue, the levels of serum lipids were markedly reduced. Conclusion: Intraventricular administration of antisense oligodeoxynucleotide to NPY Y5 receptor could significantly reduce the abdominal adipose tissue and the levels of serum lipids in diet-induced obese rats by up-regulating the level of 33-adrenergic receptor gene mRNA expression in retroperitoneal adipose tissue.