Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Glycerol-3-phosphate Acyltransferase1 Is a Model-Agnostic Node in Nonalcoholic Fatty Liver Disease: Implications for Drug Development and Precision Medicine.
ACS Omega ( IF 3.7 ) Pub Date : 2020-07-16 , DOI: 10.1021/acsomega.0c02350 Kimberly Liao 1 , Anthony J Pellicano 1 , Kai Jiang 1 , Natalia Prakash 1 , Jingsong Li 1 , Shraddha Bhutkar 1 , Zhijian Hu 1 , Quaisar Ali 1 , Itzhak D Goldberg 1 , Prakash Narayan 1
ACS Omega ( IF 3.7 ) Pub Date : 2020-07-16 , DOI: 10.1021/acsomega.0c02350 Kimberly Liao 1 , Anthony J Pellicano 1 , Kai Jiang 1 , Natalia Prakash 1 , Jingsong Li 1 , Shraddha Bhutkar 1 , Zhijian Hu 1 , Quaisar Ali 1 , Itzhak D Goldberg 1 , Prakash Narayan 1
Affiliation
![]() |
Left untreated nonalcoholic fatty liver disease (NAFLD) can progress to nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma. The observed failure of clinical trials in NASH may suggest that current model systems do not fully recapitulate human disease, and/or hallmark pathological features of NASH may not be driven by the same pathway in every animal model let alone in each patient. Identification of a model-agnostic disease-associated node can spur the development of effective drugs for the treatment of liver disease. Glycerol-3-phosphate acyltransferase1 (GPAT1) plays a pivotal role in lipid accumulation by shunting fats away from oxidation. In the present study, hepatic GPAT1 expression was evaluated in three etiologically different models of NAFLD. Compared to the sham cohort, hepatic GPAT1 mRNA levels were elevated by ∼5-fold in steatosis and NASH with fibrosis with immunofluorescent staining revealing increased GPAT1 in the fatty liver. A significant and direct correlation (r = 0.88) was observed between hepatic GPAT1 mRNA expression and severity of the liver disease. Picrosirius red staining revealed a logarithmic relation between hepatic GPAT1 mRNA expression and scar. These data suggest that hepatic GPAT1 is an early disease-associated model-agnostic node in NAFLD and form the basis for the development of a potentially successful therapeutic against NASH.
中文翻译:
3-磷酸甘油酰基转移酶1是非酒精性脂肪性肝病的模型不可知节点:对药物开发和精密医学的影响。
未经治疗的非酒精性脂肪肝疾病(NAFLD)可能会发展为非酒精性脂肪性肝炎(NASH),纤维化,肝硬化和肝细胞癌。在NASH中观察到的临床试验失败可能表明,当前的模型系统不能完全概括人类疾病,和/或NASH的标志性病理特征可能不受每种动物模型中相同途径的驱动,更不用说每个患者了。识别与模型无关的疾病相关结节可以刺激治疗肝病的有效药物的开发。3-磷酸甘油酰基转移酶1(GPAT1)通过使脂肪远离氧化而在脂质积累中起关键作用。在本研究中,肝GPAT在三种病因不同的NAFLD模型中评估了1表达。与假手术组相比,脂肪变性和NASH肝纤维化中肝GPAT 1 mRNA水平升高约5倍,免疫荧光染色显示脂肪肝中GPAT1升高。肝GPAT 1 mRNA表达与肝病严重程度之间存在显着且直接的相关性(r = 0.88)。Picrosirius红色染色显示肝GPAT 1 mRNA表达与瘢痕呈对数关系。这些数据表明,肝GPAT1是NAFLD中与疾病相关的早期模型不可知节点,并为开发潜在成功的NASH治疗药物奠定了基础。
更新日期:2020-07-28
中文翻译:
![](https://scdn.x-mol.com/jcss/images/paperTranslation.png)
3-磷酸甘油酰基转移酶1是非酒精性脂肪性肝病的模型不可知节点:对药物开发和精密医学的影响。
未经治疗的非酒精性脂肪肝疾病(NAFLD)可能会发展为非酒精性脂肪性肝炎(NASH),纤维化,肝硬化和肝细胞癌。在NASH中观察到的临床试验失败可能表明,当前的模型系统不能完全概括人类疾病,和/或NASH的标志性病理特征可能不受每种动物模型中相同途径的驱动,更不用说每个患者了。识别与模型无关的疾病相关结节可以刺激治疗肝病的有效药物的开发。3-磷酸甘油酰基转移酶1(GPAT1)通过使脂肪远离氧化而在脂质积累中起关键作用。在本研究中,肝GPAT在三种病因不同的NAFLD模型中评估了1表达。与假手术组相比,脂肪变性和NASH肝纤维化中肝GPAT 1 mRNA水平升高约5倍,免疫荧光染色显示脂肪肝中GPAT1升高。肝GPAT 1 mRNA表达与肝病严重程度之间存在显着且直接的相关性(r = 0.88)。Picrosirius红色染色显示肝GPAT 1 mRNA表达与瘢痕呈对数关系。这些数据表明,肝GPAT1是NAFLD中与疾病相关的早期模型不可知节点,并为开发潜在成功的NASH治疗药物奠定了基础。