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

Salamah Mohammad Alwahsh, Min Xu, Hatice Ali Seyhan, Shakil Ahmad, Sabine Mihm, Giuliano Ramadori, Frank Christian Schultze

Research output: Contribution to journalArticlepeer-review


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 Sprague-Dawley 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 fat degeneration 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-α 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, phospho-MAPK, caspase-9, cytochrome c and 4-hydroxynonenal was increased in the L-HFr group. Conversely, the hepatic expression of PGC-1α (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.

Original languageEnglish
Pages (from-to)1807-21
Number of pages15
JournalWorld Journal of Gastroenterology
Issue number7
Publication statusPublished - 21 Feb 2014


  • Animal Feed
  • Animals
  • Apoptosis
  • Chemokine CCL2
  • Colorimetry
  • Enzyme-Linked Immunosorbent Assay
  • Fatty Liver
  • Fructose
  • Gene Expression Regulation
  • Glucose Transporter Type 5
  • Inflammation
  • Interleukin-8
  • Leptin
  • Lipid Peroxidation
  • Lipocalins
  • Liver
  • Male
  • Oxidative Stress
  • Radioimmunoassay
  • Rats
  • Rats, Sprague-Dawley
  • Toll-Like Receptor 4


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