Rab46 and the liver

Non-alcoholic fatty liver disease (NAFLD), a chronic liver condition characterised by excessive fat in the liver, is associated with insulin resistance (as in type II diabetes), obesity and lipidaemia. The progression of NAFLD to NASH is multifactorial, however, the underlying mechanisms are not well understood and whilst a population of patients develop NASH some, with the same co-morbidities and risk factors, just have a fatty liver. Recently a pilot GWAS in patients with NAFLD looked at genetic variants significantly associated with hepatic histology. They identified rs887304 on chromosome 12 in EFCAB4B to be associated with lobular inflammation. It is important therefore to understand the contribution of CRACR2A and Rab46 to liver function. Here we utilized an Efcab4b global knockout mouse to explore the gene expression in liver.

非酒精性脂肪性肝病（Non-alcoholic fatty liver disease, NAFLD）是一种以肝脏内脂肪过度沉积为特征的慢性肝脏疾病，与胰岛素抵抗（如2型糖尿病）、肥胖及脂血症密切相关。非酒精性脂肪性肝病进展至非酒精性脂肪性肝炎（Non-alcoholic steatohepatitis, NASH）的过程为多因素介导，但目前其潜在发病机制尚未完全阐明；部分合并相同共病与危险因素的患者仅表现为单纯性脂肪肝，并未进展为NASH。近期一项针对非酒精性脂肪性肝病患者的先导性全基因组关联研究（Genome-Wide Association Study, GWAS），分析了与肝脏组织学特征显著相关的遗传变异。该研究发现12号染色体上EFCAB4B基因的rs887304位点与小叶性炎症显著相关。因此，阐明CRACR2A与Rab46对肝脏功能的调控作用具有重要意义。本研究利用Efcab4b全身敲除小鼠，探究了该基因在肝脏中的表达情况。