TITLE:
The effect of PPARδ agonists (HS00098) on serum lipid profiles in diet-induced obese rhesus monkeys
AUTHORS:
Qi-Hui Luo, Wen Zeng, Zheng-Li Chen, An-Chun Cheng, Ming-Shu Wang, Yu-Bo Shen, Chun-Mei Zhu, Feng-Jun Bi
KEYWORDS:
PPARδ Agonists; HS00098; Serum Lipid Profiles; Obese; Rhesus Monkey
JOURNAL NAME:
Journal of Biomedical Science and Engineering,
Vol.5 No.8,
July
30,
2012
ABSTRACT: Aim Activation of peroxisome proliferator-activated receptor δ (PPARδ) subtypes increases expression of genes involved in fatty acid transport and oxidation and alters adiposity in animal models of obesity and type-2 diabetes. We aim to explore the effects of peroxisome proliferator-activated receptor δ (PPARδ) subtypes on serum lipid profiles in obese rhesus monkey, especially evaluate the efficacy of investigational new drug (HS00098). Methods: First, a prototype of obese rhesus monkey was established by continuously feeding test animals a high fat diet for 2 months. Fifteen obese rhesus monkeys were randomly divided into 3 groups, and the 2 test groups were treated with GW 501516 and HS00098. The test groups were administered doses of 0.3 mg/kg for 1 month, then with 1 mg/kg for 1 month, and finally with 3 mg/kg for 1 month. The control group received placebo treatment. In each experiment, the body weight of each animal was measured and recorded initially and prior to changing the dose of the drug each month. The total cholesterol, blood glucose, triglyceride, high density lipoprotein cholesterol, low-density lipoprotein cholesterol, serum Apo-A1, Apo-B100 and insulin were tested. Results: The average body weight gain of the GW501516 and HS00098 groups was significantly lower than that of the control group. The group receiving the HS00098 treatment had a higher signifycant increase in high density lipoprotein and apo-A1 (P