study on some pharmacologic manipulations of diet-induced obesity in rats

ABSTRACT

Aim: Obesity is a major health problem that represents an energy imbalance associated with complications, including cardiovascular disease, diabetes, and an increased mortality rate. The aim of the present work was to study some pharmacological manipulations of diet-induced obesity [DIO] in rats. Subjects and The study was conducted on 60 adult male albino rats that were divided into two groups; the DIO group fed high-calorie diet [HCD] [n=48] and the normal control group [n=12] fed normal laboratory diet. After 8 weeks, DIO rats were subdivided into four subgroups [each of 12 rats] that received the lipase inhibitor [orlistat], or the PPAR-gamma agonist [rosiglitazone], or the beta3-agonist [trecadrine] or a vehicle orally for 3 weeks. After the specified period, the following obesity variables were recorded body weight, obesity index, food intake and rectal temperature. Blood samples were withdrawn for determination of serum metabolic parameters glucose, triglycerides [TG], free fatty acids [FFA], leptin and insulin levels. Rats were sacrificed; and the remaining obesity variables were measured retroperitoneal and interscapular fat as well as liver weight. The use of a HCD for 8 weeks resulted in a significant increase in all the measured obesity variables [except for rectal temperature] together with a significant increase in all the measured serum parameters as compared to rats that received normal laboratory diet. Orlistat administration for 3 weeks caused a significant decrease in all obesity variables with no significant change in food intake. A significant decrease in serum TG, FFA, insulin and leptin levels was also evident. Rosiglitazone-treated rats exhibited a significant decrease in liver weight together with a significant increase in fat pads weight and rectal temperature. Trecadrine produced significant reduction in obesity variables except for interscapular fat weight and rectal temperature that were significantly increased. Significant improvements in all serum metabolic parameters were noted with rosiglitazone and trecadrine treatment. Conclusions: From the current study, it can be concluded that lipase inhibitors and beta 3 agonists are effective in reducing body weight, while PPAR-gamma agonists are effective in improving insulin sensitivity and lipid abnormalities and so are rather effective as an adjuvant therapy to control the subsequent metabolic derangements relevant to obesity. Extrapolating these findings, especially the role of beta3-agonists, awaits further human trials before recommending it as a standard antiobesity drug