| Obesity is closely related to the occurrence and development of chronic metabolic diseases such as non-alcoholic fatty liver disease and chronic kidney disease.To investigate the molecular mechanism of obesity-induced liver and renal disease,and to find a potential target site to alleviate or reverse obesity-related metabolic diseases,the related research were conducted at cellular level.In present study,lipid-overloaded liver or renal cell models was established by oleic acid supplementation,and up-regulation of apolipoprotein J was observed in lipid-overloaded cells.Previously,we had identified the role of apolipoprotein J in hepatitis C virus –infected hepatocytes.HCV induces aberrant lipid accumulation through apolipoprotein J dependent manner,indicating that apolipoprotein J might be a universal hub in intracellular lipid accumulation.To test the hypothesis,apolipoprotein J was stably silenced in hepatic and renal epithelial cell lines.The result showed that knockdown of apolipoprotein J inhibits OA-induced liver and renal lipids accumulation.Furthermore,knockdown of apolipoprotein J restarted OA-suppressed lipophagy pathway.Lipophagy is a selective way for lipid droplet degradation by autophagy,and lipophagy is critical to maintain cellular energy homeostasis.Taken together,the study showed that fatty acid supplementation induces intracellular lipid accumulation through up-regulation of apolipoprotein J and impairs lipophagy flux,knockdown of apolipoprotein J,on the other hand,reverses OA-induced lipophagy flux.This study may reveal a new mechanism of obesity-induced chronic liver and kidney diseases,and provides new therapeutic target for the treatment of obesity-related metabolic diseases. |
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