ESPE Abstracts (2016) 86 LBP3

The Growth Hormone - Insulin Like Growth Factor I (IGF-1) System in Early Non-Alcoholic Fatty Liver Disease: From an Animal Model to a Children's Cohort

Tommaso de Giorgisa, Melanie Penkea, Susanne Schustera, Nico Grafeb, Alexander Kielb, Thomas Karlasc, Johannes Weigandc, Mandy Vogelb, Antje Gartena, Körner Antjea,b & Wieland Kiessa,b


aCenter for Pediatric Research, University Hospital for Children and Adolescents Leipzig, University of Leipzig, Leipzig, Germany; bLIFE Leipzig Research Centre for Civilization Diseases, University of Leipzig, 04103 Leipzig, Germany; cDepartment of Medicine, Division of Gastroenterology and Rheumatology, University Hospital Leipzig, Leipzig, Germany


Background: Non-alcoholic fatty liver disease (NAFLD) represents one of the most common obesity complications and can progress to non-alcoholic stetohepatitis (NASH). NASH is associated with lower insulin like growth factor I (IGF-1) and IGFBP-3, however no data are available regarding the growth hormone (GH)-IGF-I axis in early stage of NAFLD, characterised by hepatic steatosis.

Objective and hypotheses: We aimed to investigate the GH-IGF-1 pathway in a diet-induced animal model of liver steatosis and proved the data in a human cohort of obese and lean children.

Method: C57BL/6 mice (n=12) were fed with a standard diet (ND) or a high fat diet (HFD) (n=12) for 11 weeks. The hepatic lipid content was measured by MAS spectroscopy. Immunoblot and qPCR analyses were used to study activation of the hepatic GH-IGF-1 system. In serum of obese (n=77) and normal-weight children (n=88), IGF-1 and IGFBP-3 were measured. To estimate the liver steatosis, transient elastography (FibroScan®, Echosens™) was performed to measure the controlled attenuated parameter (CAP).

Results: HFD mice presented a higher body weight and hepatic lipid content compared to ND mice (p<0.005). In addition, a lower hepatic expression of phosphorylated-STAT-5B, janus kinase-2 (pJAK2) and IGF-1 (−1.56, −2.7 and −1.9-fold) was found in HFD compared to ND mice. In obese children, higher CAP values were found compared to normal weight children (211.8±76.7 vs 187.82±37.7 dB/m, p=0.0002), indicating a steatotic phenotype. In addition, obese subjects presented lower IGF-1 compared to controls (p=0.007). After categorizing subjects according to tertiles of CAP, the IGF-1-SDS decreased significantly across the tertiles (p<0.04). An inverse correlation was found between IGF-1-SDS and CAP (p=0.014, r=−0.254).

Conclusion: The GH-IGF-1 axis is impaired already in early NAFLD. In particular, IGF-1 could be an early marker to define the hepatic steatotic phenotype.