DIFFERENTIAL EFFECTS OF PEROXISOME PROLIFERATOR-ACTIVATOR RECEPTOR (PPAR) ALPHA AND GAMMA AGONISTS ON BODY WEIGHT AND ADIPOSE DEPOTS IN FRUCTOSE FED WISTAR RATS

Emilija Atanasovska; Kristina Pavlovska; Krume Jakjovski; Kalina Gjorgjievska; Dragica Zendelovska; Marija Petrushevska; Irfan Ahmeti; Dimce Zafirov; Nikola Labacevski

Emilija Atanasovska MD, PhD
Kristina Pavlovska Department of Preclinical and Clinical Pharmacology and Toxicology, Medical Faculty, Skopje
Krume Jakjovski
Kalina Gjorgjievska Department of Preclinical and Clinical Pharmacology and Toxicology, Medical Faculty, Skopje
Dragica Zendelovska
Marija Petrushevska Department of Preclinical and Clinical Pharmacology and Toxicology, Medical Faculty, Skopje
Irfan Ahmeti University Clinic of Endocrinology, Diabetes and Metabolic Disorders, Faculty of Medicine, Skopje
Dimce Zafirov Department of Preclinical and Clinical Pharmacology and Toxicology, Medical Faculty, Skopje
Nikola Labacevski Department of Preclinical and Clinical Pharmacology and Toxicology, Medical Faculty, Skopje

Abstract

Aims: To investigate the effect of fenofibrate (PPAR-alpha agonist) and rosiglitazone (PPAR-gamma agonist) on body weight and adipose depots in an experimental model of the metabolic syndrome.

Methods: Metabolic syndrome was induced in 48 male Wistar rats by adding a fructose in drinking water (10% solution) for 12 weeks. During the last 4 weeks, 16 rats were treated with fenofibrate (100 mg/kg/day), 16 rats were treated with rosiglitazone (5 mg/kg/day) by intragastric tube, while the remaining 16 did not receive any medication (fructose group). Another control group of 16 rats consumed standard rat chow and water for 12 weeks.

Results: Chronic fructose administration for 12 weeks significantly increased the body weight (p<0.05), as well as the weight of the measured fat pads: perirenal (p<0.001) and epididymal (p<0.001) as representatives of the visceral adipose depots and the inguinal pads (p<0.05) as a representative of the subcutaneous adipose depots compared to the control group. This was accompanied with a decrease of the subcutaneous/visceral fat ratio. Treatment with fenofibrate over the final 4 weeks significantly decreased the body weight (p<0.001) and the weight of the epididymal, perirenal and inguinal fat pads (p<0.001 for all parameters), without changes of the subcutaneous/visceral fat ratio.

On the other hand, rosiglitazone promoted weight gain. Treatment with this PPAR-gamma agonist significantly decreased the weight of the epididymal (p<0.01) and perirenal (p<0.05) pads, but increased the weight of the inguinal fat pads (p<0.001) compared to the fructose group, which led to an increase of the subcutaneous/visceral fat ratio.

Conclusion: This study indicates that treatment with the PPAR-alpha agonist fenofibrate decreases body weight and reduces the fat depots, whereas PPAR-gamma agonist promotes weight gain and a body fat redistribution from visceral towards subcutaneous depots in an animal nutritive model of the metabolic syndrome.

Key words: fructose, fenofibrate, rosiglitazone, PPAR, metabolic syndrome, body weight