Study for therapeutic effect of hepatocyte specific Pten deficiency on severe obesity.

我们的目的是研究肝细胞特异性Pten缺乏是否可以通过激活肝脏脂肪生成来改善瘦素缺乏的ob/ob小鼠的肥胖。为此，我们将肝细胞特异性Pten缺失小鼠与瘦素缺失小鼠配对，建立了ob/ob/AlbCre/Pten^<flox/flox>小鼠。ob/ob小鼠（ob/ob组）、ob/ob/AlbCre/Pten^<flox/flox>小鼠（双KO组）、AlbCre/Pten^<flox/flox>小鼠（KO组）、野生型小鼠（WT组）于断奶后40周处死，测定体重、睾丸或卵巢周围脂肪组织重量、肝脏重量、肝脏甘油三酯含量、血清转氨酶水平和血清总ROS水平。此外，我们通过western blot分析研究了Akt的激活情况，并通过实时荧光定量PCR检测了各种基因特别是β-氧化相关基因的表达。结果是肝细胞特异性Pten缺乏通过激活肝脏脂肪生成改善瘦素缺乏的ob/ob小鼠的肥胖。

Our aim is to investigate whether hepatocyte-specific Pten deficiency can improve obesity in the leptin-deficient ob/ob mouse by activating lipogenesis in the liver. For this purpose, we have mated hepatocyte-specific Pten deficient mouse with leptin-deficient ob/ob mouse and established ob/ob/AlbCre/Pten^<flox/flox> mouse. ob/ob mice (ob/ob group), ob/ob/AlbCre/Pten^<flox/flox> mice (double KO group), AlbCre/Pten^<flox/flox> mice (KO group), Wild type mice (WT group) were sacrificed at 40 weeks just after weaning and measured body weight, fat tissue weight around testis or ovary, liver weight, triglyceride content in the liver, serum transaminase level and total ROS level in serum. Moreover we investigated Akt activation by western blot analysis and examined the expression of various genes especially related to β-oxidation by quantitative real-time PCR. The result is Hepatocyte-specific Pten deficiency improved obesity in the leptin-deficient ob/ob mouse by activating lipogenesis in the liver.