Objective: To study the efficacy of antisense oligonucleotide of neuropeptide Y (NPY) Y5 receptor on treating hyperleptinemia by intracerebral ventricular administration in diet-induced obese rats.Methods: The obese rats were prepared by feeding a high-nutritive diet for 7 weeks. The lateral ventricle of obese rats was cannulated. Either 10 μl of different neuropeptide Y Y5 receptor oligodeoxynucleotide, including antisense, sense and missense oligodeoxynucleotide (5 g/L) or 10 μl saline was administered into the ventricle through cannula three times per day in every rat. Two days later the rats were slaughtered .The weights of both retroperitoneal and epididymal adipose tissues were measured, and the serum insulin and leptin were detected by radioimmunoassay method and the murine leptin ELISA kit respectively. Results: ①The level of serum was significantly higher in experimental rats than that in normal rats. Similarly, the level of serum insulin and the weights of both retroperitoneal and epididymal adipose tissues were increased in experimental rats. ②After the diet-induced obese rats were intraventricularly administered with NPY Y5 receptor antisense oligodeoxynucleotide, the levels of serum leptin and insulin were significantly decreased and combined with the reduction of weight in retroperitoneal adipose tissue. There was, however, no significant difference in the weight of epidymal adipose tissue between pre-treated and post-treated duration. ③There was significant positive correlation among the level of serum leptin, the level of serum insulin and the weight of retroperritoneal adipose tissue in diet-induced obese rats. Conclusion: Intracerebral ventricular administration of antisense oligodeoxynucleotide of neuropeptide Y Y5 receptor may alleviate hyperleptinemia in diet-induced obese rats and decrease the weight of retroperitoneal adipose tissue and the level of serum insulin.
Objective: To study the role of β3-adrenergic 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 5 μg/μl NPY Y5 receptor antisense or 10 μl missense oligodeoxynucleotide or saline of 10 μl 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: ①The 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. ②After 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 β3-adrenergic receptor gene mRNA expression in retroperitoneal adipose tissue.
