Adult-onset loss of hepatocyte growth hormone receptor (GHR) signaling increases steatosis, associated with enhanced glucokinase activity, de novo lipogenesis (DNL) and pathway selective hepatic insulin resistance

RNA-seq analysis of livers from control mice, mice with adult onset, hepatocyte-specific GH receptor (GHR) deficiency, and GHR-deficient mice combined with IGF1 expression or expression of constitutively active ('CA') STAT5b. This dataset is part of a large study showing that adult-onset loss of hepatocyte GHR signaling increases steatosis, associated with enhanced glucokinase activity, de novo lipogenesis (DNL) and pathway selective hepatic insulin resistance. We analyzed total RNA from male livers (6 mice/group) from GHR intact-control mice and adult-onset, specific GHR knockdown mice, without (aHepGHRkd) or with hepatic reconstitution of IGF1 (aHepGHRkd + 2.0*E11 AAV8-TBGp-rIGF1) or STAT5bCA (aHepGHRkd + 0.75*E11 AAV8-TBGp-STAT5bCA)

本研究针对对照组小鼠、成年起病肝细胞特异性生长激素受体（GHR）缺陷小鼠，以及联合表达胰岛素样生长因子1（IGF1）或组成型激活（'CA'）信号转导与转录激活因子5b（STAT5b）的GHR缺陷小鼠的肝脏开展RNA-seq分析。该数据集隶属于一项大型研究，研究证实成年起病的肝细胞GHR信号通路缺失可加剧肝脏脂肪变性，且伴随葡萄糖激酶活性增强、从头脂肪生成（de novo lipogenesis, DNL）以及通路选择性肝脏胰岛素抵抗。我们对各组雄性小鼠的肝脏总RNA进行了分析，每组包含6只小鼠，样本涵盖GHR完整的对照小鼠，以及成年起病特异性GHR敲低小鼠（aHepGHRkd）：其中未接受额外重组表达干预的为aHepGHRkd组，另有两组分别接受了肝脏IGF1重组表达干预（aHepGHRkd + 2.0*E11 AAV8-TBGp-rIGF1）与STAT5bCA重组表达干预（aHepGHRkd + 0.75*E11 AAV8-TBGp-STAT5bCA）。