Endocrine Abstracts

Background: IGF1 is mainly produced in the liver and it induces beneficial effects on many systems. However, the role of IGF1 on the own liver is poorly understood, probably due to the fact that healthy hepatocytes barely express IGF1 receptors. Previous works in our group showed that IGF1 supplementation induces beneficial actions in cirrhosis, including antioxidant, anti-inflammatory and antifibrogenic effects. Based on these data the aim of this work was to deep into the mechanisms of IGF1 in hepatoprotection using a novel murine model of partial deficiency of IGF1 without previous pathology¹.

Materials and methods: Livers from heterozygous (Igf1^+/−) 5 months old mice (Hz, n=10) were compared to those from homozygous Igf1^+/+ (WT, n=10, same age) by assessing hepatic gene expression (by microarray and further quantitative PCR) of IGF1-related factors, antioxidant enzymes, inflammatory response molecules, heat shock proteins and cell death markers. The effect of the replacement therapy with low doses of rhIGF1 (2 μg/100 g Bw per day, for 10 days, s.c.) was evaluated in parallel (group Hz+IGF, n=10, same age). Complementarily, the marker of oxidative damage malondialdehyde (MDA), was measured.

Results: Firstly, we confirmed that the reduced Igf1 gene expression correlated with low circulating levels and interestingly IGF1 replacement therapy restored Igf1 gene expression suggesting a novel role of IGF1 in autoregulation. Compared to controls, Hz mice showed an increased hepatic lipid peroxidation, overexpression of genes related to pro-inflammatory pathways, hypoexpression of antioxidant enzymes and apoptosis inhibitory factors genes. IGF1 supplementation normalized lipid peroxidation and improved gene expression of majority of these factors.

Conclusion: All these data together suggest that IGF1 deficiency increases liver vulnerability to oxidative damage and offer the possibility to develop new therapeutic strategies using IGF1 as a hepatoprotective factor.

1. Castilla-Cortazar I et al. 2013 J Physiol Biochem.