Diet high in fructose leads to an overexpression of lipocalin-2 in rat fatty liver

摘要

AIM:To explore lipocalin-2(LCN-2)expression and its possible role and mechanism(s)of production in rat models of diet-inducible fatty liver.METHODS:Fatty liver was triggered in male SpragueDawley rats fed either with liquid Lieber-DeCarli(LDC)or LDC+70%cal fructose(L-HFr)diet for 4 or 8 wk.Chow-nourished animals served as controls.Hepatic expression of LCN-2 and other metabolic and inflammatory mediators was assessed by quantitative reverse transcription polymerase chain reaction and Western blotting.Serum LCN-2,fasting leptin,and lipid profile were evaluated via Enzyme-Linked Immunosorbent Assay,Radioimmunoassay,and colorimetric assays,respectively.The localization of LCN-2 in the liver was detected by using immunofluorescence staining.Furthermore,HE stain was used to evaluate hepatic fatdegeneration and inflammation.RESULTS:Both LDC-fed and L-HFr-fed rat histologically featured fatty liver.In the liver,mRNA transcriptions of Mcp-1,a2-m,Il-8 and Glut5 were increased in the L-HFr group at both time points(P<0.001),while the transcription of Tlr4,Inos,and Tnf-a was significantly up-regulated at week 4.Interestingly,hepatic Lcn-2 expression was 90-fold at week 4 and 507-fold at week 8 higher in L-HFr-subjected rats vs control(P<0.001).In contrast to HDL-cholesterol,systemic levels of LCN-2,fasting leptin and triglycerides were elevated in the L-HFr regimen(P<0.001).Moreover,protein expression of hepatic LCN-2,CD14,phosphoMAPK,caspase-9,cytochrome c and 4-hydroxynonenal was increased in the L-HFr group.Conversely,the hepatic expression of PGC-1a(a mitochondrial-biogenic protein)was reduced in the L-HFr category at week 8.The localization of LCN-2 in the liver was predominantly restricted to MPO+granulocytes.CONCLUSION:Fructose diet up-regulates hepatic LCN-2 expression,which correlates with the increased indicators of oxidative stress and mitochondrial dysfunction.The LCN-2 may be involved in liver protection.