The effect of insulin-like growth factor-II on Lcn13 expression and hepatic liver metabolism

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 88-108-GHRH, GH & IGF Biology & Signaling
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-102
Mary Frances Lopez*1, Gali Reddy2, Uzoamaka Agubokwu3 and Joel N Hirschhorn4
1Harvard Medical School, Department of Medicine, Boston, MA, 2Harvard Medical School, Boston, MA, 3Children's Hospital, Boston, MA, 4Division of Endocrinology, Boston Children's Hospital and Program in Medical and Population Genetics, Broad Institute, Harvard Medical School, Boston, MA
Obesity is frequently complicated by hepatic statosis; however, the underlying mechanism of abnormal hepatic lipid metabolism is not completely understood.  Insulin-like growth factor-II (IGF2) is an insulin-related protein involved in growth and metabolism. We have previously demonstrated that Igf2 plays an important role in carbohydrate metabolism in the fetus.  The present study aims to define the role of Igf2 in hepatic lipid metabolism.  Histological data showed that Igf2-deficient livers contained high lipid concentrations.  Microarray experiments were performed in livers collected from Igf2 wild-type (Igf2+/+) and Igf2 knockout (Igf2-/-) adult mice (N=3 each).  We analyzed the gene expression data using classical single gene analysis and gene set enrichment analysis (GSEA).  The most significant down-regulated individual gene was lipocalin-13 (Lcn13), a gene that functions as insulin sensitizer and a protector against hepatic steatosis.   Livers of Igf2-/- mice had a 5-fold decrease in Lcn13 expression compared to those of Igf2+/+mice (P < 0.02).  Quantitative RT-PCR in independent samples showed a 8-fold decrease in Lcn13 expression in Igf2-/- livers, confirming the microarray results. The most significant differentially expressed gene set in GSEA analysis was NO1 (Biocarta, FDR q-value < 0.05).  This gene set contained several genes involved in lipid metabolism such as Prkar1b and Slc7a.    Together, these gene expression studies suggest that IGF2 may alter hepatic lipid metabolism by regulating genes such as Lcn13 and other pathways involved in lipid homeostasis.  Further studies to determine how IGF2 regulates hepatic lipid metabolism and Lcn13 expression, including in the setting of obesity, will potentially help us understand the basic mechanisms by which the liver accumulates fat and could help in future treatments of this common complication of obesity.

Nothing to Disclose: MFL, GR, UA, JNH

*Please take note of The Endocrine Society's News Embargo Policy at

Sources of Research Support: This work was supported by the NIH supplement grant R01 DK075787.