Pathological and biochemical investigation of the effects of L-carnitine and gemfibrozil on peroxisome proliferator activated receptors (PPARS) and lipidosis in rabbits on a high-fat diet

Abstract

Obesity and fatty liver is a worldwide health problem in human with detrimental consequences where many investigations are undertaken to overcome this problem. In this study, gemfibrozil and L-carnitine were evaluated in prevention of obesity and lipidosis. The study involved 56 New-Zealand Albino rabbits, divided into 8 equal groups (n=7). The groups were as follow; group I (normal diet), II (normal diet +gemfibrozil), III (normal diet+L-carnitine) and IV (normal diet+gemfibrozil+L- carnitine), V (high fat diet), VI (high fat diet+gemfibrozil), VII (high fat diet+L- carnitine) and VIII (high fat diet+gemfibrozil+L-carnitine). Animals were blood sampled and wieght weekly during the experiment and at the end of the experiment for determination of biochemical parameters (glucose, total lipid). All rabbits were euthanised for histopathological examination and for distrubition of peroxisome proliferator activated receptors (PPARs) in tissues by immunohystochemistry. Gemfibrozil and L-carnitin treatment in rabbits given high fat diet resulted in statistically significant decrease in total lipid when compared to those only received high fat diet. Beta oxidation of high fat diet group was significantly higher than that of groups additionally received gemfibrozil and L-carnitine. Immunohistochemistry revealed an increase in PPAR, PPAR-α and β but not PPAR-γ expression in high fat diet group. On the contrary, L-carnitin administration had no effect on tissue PPAR expression. PPAR-α expression differed between groups received gemfibrozil and high fat diet and those did not. The most marked macroscopy finding was abdominal fat increase in high fat diet group (group V). On the other hand gemfibrozil administration resulted in significant abdominal fat decrease. Furthermore decreased abdominal fat was marked in gemfibrozil and L-carnitine given animals (group VIII) when compared to other groups. In conclusion, gemfibrozil and L-carnitine administration alleviated abdominal and hepatic fattening. Gemfibrozil also caused a significant increase in PPAR-α expression in the liver. It may be of use in avoiding abdominal fat (obesity) due to high fat diet by use of gemfibrozil, a synthetic PPAR-a ligand, and L-carnitine.