DPP-4 Inhibitor and PPAR gamma Agonist Restore the Loss of CA1 Dendritic Spines in Obese Insulin-resistant Rats

作者：Sripetehwandee Jirapas; Pipatpiboon Noppamas; Pratchayasakul Wasana; Chattipakorn Nipon; Chattipakorn Siri**** C^*

来源：Archives of Medical Research, 2014, 45(7): 547-552.

DOI：10.1016/j.arcmed.2014.09.002

• Vildagliptin
• Pioglitazone
• Dendritic spines
• High-fat diet
• Insulin resistance

Background and Aims. Obesity induced by high-fat diet (HFD) impaired brain insulin receptor function, caused cognitive decline as well as reduced dendritic spine density. Previous studies suggested that dipeptidyl peptidase IV (DPP-4) inhibitor and peroxisome proliferator-activated receptor-gamma (PPAR gamma) agonist exerted the neuroprotective effects in obese insulin-resistant rats. However, the effects of these drugs on dendritic spines in obese insulin-resistant rats have not yet been investigated. In the present study, we determined the effects of DPP-4 inhibitor and PPAR gamma agonist on dendritic spines density of obese insulin-resistant rats caused by HFD. %26lt;br%26gt;Methods. Male Wistar Rats were divided into two groups. Animals in each group were fed with normal diet (ND) or HFD for 12 weeks. After then, rats in each group were subdivided into three subgroups to receive either vehicle or vildagliptin (3 mg/kg/day) or pioglitazone (10 mg/kg/day) for 3-4 weeks. At the end of the experiment, the metabolic parameters and density of dendritic spines in CA1 hippocampus were determined. %26lt;br%26gt;Results. We found that HFD-fed rats caused peripheral insulin resistance as well as the reduction of the density of dendritic spines in CA1 hippocampus. Treatment with both DPP-4 inhibitor and PPAR gamma agonist in HFD-fed rats improved insulin sensitivity as well as increased the number of dendritic spines in CA1 hippocampus. Moreover, both drugs have equally improved this deterioration. %26lt;br%26gt;Conclusion. Our findings indicate that DPP-4 inhibitor and PPAR gamma agonist restored the reduction of dendritic spines caused by HFD, suggesting the beneficial roles of DPP-4 inhibitors and PPAR gamma agonists in neurodegenerative disorders.

• 出版日期2014-10