GSE154217 GH directly inhibits steatosis and liver injury in a sex-dependent and IGF1-independent manner

Contributor : R D KinemanSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusA reduction in hepatocyte GH-signaling promotes non-alcoholic fatty liver disease (NAFLD). However, debate remains as to the relative contribution of the direct effects of GH on hepatocyte function versus indirect effects, via alterations in IGF1. To test the isolated role of hepatocyte GHR signaling, independent of changes in IGF1, we reconstituted IGF1 in mice with adult-onset, hepatocyte-specific GHR knockdown (aHepGHRkd) using a vector expressing rat IGF1 targeted specifically to hepatocytes. Compared to GHR-intact mice, aHepGHRkd reduced circulating IGF1 and elevated GH. In male aHepGHRkd mice, the shift in IGF1/GH did not alter plasma glucose or NEFA, but was associated with increased insulin, enhanced systemic lipid oxidation and reduced white adipose tissue (WAT) mass. Livers of male aHepGHRkd exhibited steatosis associated with increased de novo lipogenesis, hepatocyte ballooning and inflammation. In female aHepGHRkd mice, hepatic GHR protein levels were not detectable, but moderate levels of IGF1 were maintained, with minimal alterations in systemic metabolism and no evidence of steatosis. Reconstitution of hepatocyte IGF1 in male aHepGHRkd lowered GH and normalized insulin, whole body lipid utilization and WAT mass. However, IGF1 reconstitution did not reduce steatosis and had minimal effects on liver injury. RNAseq analysis showed IGF1 reconstitution did...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research