title: Diet high in fructose leads to an overexpression of lipocalin-2 in rat fatty liver.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Salamah Mohammad Alwahsh, Hatice Ali Seyhan, Shakil Ahmad, Sabine Mihm, Giuliano Ramadori, Frank Christian Schultze, Department of Gastroenterology and Endocrinology, University Medical Center Goettingen, 37075 Goettingen, Germany.
authors.forename: Salamah Mohammad
authors.initials: SM
authors.lastname: Alwahsh
authors.affiliation: Salamah Mohammad Alwahsh, Hatice Ali Seyhan, Shakil Ahmad, Sabine Mihm, Giuliano Ramadori, Frank Christian Schultze, Department of Gastroenterology and Endocrinology, University Medical Center Goettingen, 37075 Goettingen, Germany.
authors.forename: Min
authors.initials: M
authors.lastname: Xu
authors.affiliation: Salamah Mohammad Alwahsh, Hatice Ali Seyhan, Shakil Ahmad, Sabine Mihm, Giuliano Ramadori, Frank Christian Schultze, Department of Gastroenterology and Endocrinology, University Medical Center Goettingen, 37075 Goettingen, Germany.
authors.forename: Hatice Ali
authors.initials: HA
authors.lastname: Seyhan
authors.affiliation: Salamah Mohammad Alwahsh, Hatice Ali Seyhan, Shakil Ahmad, Sabine Mihm, Giuliano Ramadori, Frank Christian Schultze, Department of Gastroenterology and Endocrinology, University Medical Center Goettingen, 37075 Goettingen, Germany.
authors.forename: Shakil
authors.initials: S
authors.lastname: Ahmad
authors.affiliation: Salamah Mohammad Alwahsh, Hatice Ali Seyhan, Shakil Ahmad, Sabine Mihm, Giuliano Ramadori, Frank Christian Schultze, Department of Gastroenterology and Endocrinology, University Medical Center Goettingen, 37075 Goettingen, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Mihm
authors.affiliation: Salamah Mohammad Alwahsh, Hatice Ali Seyhan, Shakil Ahmad, Sabine Mihm, Giuliano Ramadori, Frank Christian Schultze, Department of Gastroenterology and Endocrinology, University Medical Center Goettingen, 37075 Goettingen, Germany.
authors.forename: Giuliano
authors.initials: G
authors.lastname: Ramadori
authors.affiliation: Salamah Mohammad Alwahsh, Hatice Ali Seyhan, Shakil Ahmad, Sabine Mihm, Giuliano Ramadori, Frank Christian Schultze, Department of Gastroenterology and Endocrinology, University Medical Center Goettingen, 37075 Goettingen, Germany.
authors.forename: Frank Christian
authors.initials: FC
authors.lastname: Schultze
mesh_terms: D000821:Animal Feed; D000818:Animals; D017209:Apoptosis; D018932:Chemokine CCL2 / Q000378:metabolism; D003124:Colorimetry; D004797:Enzyme-Linked Immunosorbent Assay; D005234:Fatty Liver / Q000378:metabolism*; D005632:Fructose / Q000378:metabolism*; D005786:Gene Expression Regulation; D051296:Glucose Transporter Type 5 / Q000378:metabolism; D007249:Inflammation; D016209:Interleukin-8 / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D015227:Lipid Peroxidation; D000071068:Lipocalin-2; D054834:Lipocalins / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D051296:Glucose Transporter Type 5; D016209:Interleukin-8; C097278:Lcn2 protein, rat; D020738:Leptin; D000071068:Lipocalin-2; D054834:Lipocalins; C495727:Slc2a5 protein, rat; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D005632:Fructose
keywords: Endotoxins; Inflammation; Lipopolysaccharide; Metabolic syndrome; Mitochondrial dysfunction; Non-alcoholic fatty liver disease; Oxidative stress