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

Year 2022, Volume: 7 Issue: 3, 346 - 360, 31.12.2022

Mehmet Çitil , Recai Tunca , Erdoğan Uzlu , Mahmut Karapehlivan , Yasemen Adalı , Kürşat Yapar , Hüseyin Avni Eroğlu , Ekin Emre Erkılıç , Mustafa Makav , Hidayet Metin Erdoğan

https://doi.org/10.31797/vetbio.1136444

Abstract

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.

Keywords

Gemfibrozil, hepatic lipidosis, L-carnitine, obesity, PPARs, rabbits

Supporting Institution

This study was financially supported The Scientific and Technical Research Council of Turkey (Project Number 106 O 160).

Project Number

Project Number 106 O 160

Thanks

We sincerely thank The Scientific and Technical Research Council of Turkey as a study team for providing financial support.

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