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
Authors: ÇİTİL Mehmet , TUNCA Recai , UZLU Erdoğan , KARAPEHLİVAN Mahmut , ADALI Yasemen , YAPAR Kürşat , EROĞLU Hüseyin Avni , ERKILIÇ Ekin Emre , MAKAV Mustafa , ERDOĞAN Hidayet Metin 
Published: December 2022

Obesity and fatty liver is a widespread growing health problem in human with detrimental consequences that encouraged researchers to find ways to overcome it. In this study, gemfibrozil and L-carnitine were evaluated in prevention of obesity and hepatic lipidosis also the role of L-carnitine in avoiding side effects of gemfibrozil was investigated.
The study involved 56 New-Zealand Albino rabbits, divided into 2 main groups and then subdivided into 4 equal groups (n=7). The groups I (normal diet), II (normal diet+gemfibrozil), III (normal diet+L-carnitine) and IV (normal diet+gemfibrozil+L-carnitine) received normal diet and the groups V (fat rich diet), VI (fat rich diet+gemfibrozil), VII (fat rich diet+L-carnitine) and VIII (fat rich diet+gemfibrozil+L-carnitine) received fat rich diet for 8 weeks.
Animals were blood sampled and wieght weekly during the experiment and at the end of the experiment for determination of biochemical (HDL, High-density lipoproteins; LDL, Low-density lipoprotein; VLDL, Very low-density lipoprotein; ALT, Alanine amino transferase; AST, Aspartate aminotransferase; GGT, Gamma glutamyltransferase; GLDH, Glutamate lactate dehydrogenase; LDH, Lactate dehydrogenase) and oxidative stress (MDA, Malondialdehyde; GSH, Reduced gluthation; NO, Nitric oxide; SOD, Superoxide dismutase) parameters. All rabbits were euthanised for histopathological examination and for distrubition of Peroxisome proliferator activated receptors (PPARs) in tissues by immunohystochemistry.
Liver enzymes increased in fat rich diet group throughout the study. Addition of gemfibrozil and L-carnitin in fat rich diet resulted in statistically significant decreasein lipid profile when compared to those only received fat rich diet. Beta oxidation of fat rich 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 fat rich diet group. On the contrary L-carnitin administration did have any effect on tissue PPAR expression. PPAR-α expression differed between groups received gemfibrozil and fat rich diet and those did not. Fat rich diet increased MDA level while decreased GSH and catalase. Addition of gemfibrozil and L-carnitine to fat rich diet significantly decreased MDA level and increased antioxidants. The most marked macroscopy finding was abdominal fat increase in fat rich 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 and improved lipid profile. 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 by use of gemfibrozil, a synthetic PPAR-a ligand, and L-carnitine.