Z Gastroenterol 2013; 51 - P_3_01
DOI: 10.1055/s-0032-1331996

Lipocalin-2 is a biomarker in rat fatty liver induced by fructose-enriched diet

SM Alwahsh 1, M Xu 2, G Ramadori 1, FC Schultze 1
  • 1University Medical Center Göttingen, Gastroenterology and Endocrinology, Göttingen, Germany
  • 2University Medical Center Göttingen, General and Visceral Surgery, Göttingen, Germany

Introduction and aims:

Hepatic steatosis is associated with metabolic syndrome; and through NASH, it could progress to cirrhosis and liver carcinoma. Since lipocalin-2 (LCN2) influences inflammatory and metabolic processes, we intended to examine LCN2 as a possible biomarker in various rat models of diet-triggered fatty liver.

Methods:

Fatty liver was induced in male Sprague Dawley rats fed with liquid Lieber-DeCarli (LDC) or LDC + 70% kcal fructose (L-HFr) diets for 4 or 8 weeks. Control group was fed with standard chow. Liver histology was studied for inflammation and fat degeneration by Hematoxylin-Eosin stain. Hepatic mRNA of LCN2 as well as the inflammatory mediators MCP-1, CCR2, NF-κB, TNF-α and STAT3 were quantified using RT-PCR. Western blots for both serum and hepatic LCN2 protein were performed. Furthermore, serum LCN2 level was verified by ELISA. Biochemical parameters like fasting serum leptin and hepatic leptin receptor (LEP-R) were studied by RIA and RT-PCR, respectively. In addition, transaminases and triglycerides levels were examined in the plasma.

Results: Treated rats developed hepatic fat deposit accompanied with mild periportal inflammation, featuring a fatty liver. Contrary to standard chow or LDC diet, L-HFr regimen revealed significantly up regulated hepatic LCN2 mRNA confirmed by the enhanced hepatic and serum LCN2 protein (p<0.05). Although mRNA levels of hepatic MCP-1, CCR2, TNF-α, NF-κB, and STAT3 were also significantly increased in fructose-subjected animals, they did not overwhelm the increased LCN2 to this extent. The changes in hepatic transaminases were mild. The magnitude of food intake, hepatic LEP-R mRNA, as well as of fasting serum leptin and triglycerides was the highest in L-HFr fed rats (p<0.05).

Conclusion: The present study suggests LCN2 as a biomarker for fructose-induced fatty liver. The elevated LCN2 level was mainly attributed to metabolic changes more likely than inflammatory alteration. The increased fasting serum leptin level and food intake may indicate fructose-mediated leptin resistance.