Naringin improves lipid metabolism in a tissue-engineered liver model of NAFLD and the underlying mechanisms.
AIMS
Nonalcoholic fatty liver disease (NAFLD) is a lipid metabolism disorder. Naringin (a main active ingredient in Ganshuang granules) is a flavanone that has been demonstrated to exert hepatoprotective and antifibrotic effects. The present study aimed to use a novel tissue-engineered fatty liver model to assess the effects and mechanisms of naringin on NAFLD.


MAIN METHODS
Intracellular triglyceride (TG) was examined by oil red O staining and commercial kits. The proteins associated with lipid metabolism were measured by western blotting and/or qPCR. Very low-density lipoprotein (VLDL) was measured by ELISA. A CCK8 assay was used to assess the cytotoxicity of naringin. Molecular docking was used to predict the interactions and binding patterns between naringin and target proteins.


KEY FINDINGS
Naringin significantly reduced intracellular TG accumulation by 52.7% in tissue-engineered fatty (TEF) livers, and also the level of pyruvate dehydrogenase kinase 4. Naringin downregulated CD36 and proliferator activated-receptor γ expression, reducing the uptake of FFAs; naringin also downregulated de novo liposynthetases by reducing acetyl CoA carboxylase, fatty acid synthetase etc. in TEF livers. Moreover, naringin increased the expression of proliferator activated-receptor α (PPAR-α) and carnitine palmitoyltransferase 1 to improve the oxidation of fatty acids. The levels of VLDL secreted from TEF livers were reduced by 24.7% after naringin treatment. Molecular docking analyses determined the bioactivity of naringin through its specific binding to CD36 and PPAR-α.


SIGNIFICANCE
Naringin improved lipid metabolism disorders in TEF livers by reducing fatty acid uptake and de novo lipogenesis and increasing fatty acid oxidation. CD36 and PPAR-α might be specific targets of naringin.
['Zhang|Xiaohui|X|', 'Zhang|Yizhi|Y|', 'Gao|Wen|W|', 'Guo|Zhihao|Z|', 'Wang|Kun|K|', 'Liu|Shuang|S|', 'Duan|Zhongping|Z|', 'Chen|Yu|Y|']
D000103:Acetyl-CoA Carboxylase D000818:Animals D004195:Disease Models, Animal D005227:Fatty Acids D044950:Flavanones D056945:Hep G2 Cells D006801:Humans D050356:Lipid Metabolism D050155:Lipogenesis D008079:Lipoproteins, VLDL D008099:Liver D008297:Male D062105:Molecular Docking Simulation D065626:Non-alcoholic Fatty Liver Disease D010084:Oxidation-Reduction D047493:PPAR alpha D051381:Rats D017207:Rats, Sprague-Dawley D014280:Triglycerides
Naringin Lipid metabolism Tissue-engineered liver Nonalcoholic fatty liver disease