Liu Xia, Guo Yaoyao, Li Zhaozhen, Gong Yanling
Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, China.
Shandong Luoxin Pharmaceutical Group Stock Co., Ltd., Preparation Department, Linyi, 276000 China.
Iran J Basic Med Sci. 2020 Sep;23(9):1191-1196. doi: 10.22038/ijbms.2020.45356.10555.
Ghrelin is a brain-gut peptide involved in substance and energy metabolism. To confirm the hypothesis that ghrelin might be involved in non-alcoholic fatty liver disease (NAFLD), a rat NAFLD model was established and the changes of ghrelin were explored.
The rats were divided into control and NAFLD groups. The rats in the NAFLD group were fed a high-fat-high-cholesterol (HFHC) diet for 8 weeks. Total ghrelin (TG), acylated ghrelin (AG), unacylated ghrelin (UAG), and hypothalamic AG and its receptor GHSR-1a expression were detected using ELISA, RIA, RT-PCR, and Western blot, respectively.
Plasma UAG, TG, and the ratio of UAG to AG (UAG/AG) decreased, while protein and mRNA expression of hypothalamic AG and growth hormone secretagogue receptor-1a (GHSR-1a) increased in NAFLD (0.01). Plasma UAG and UAG/AG were negatively associated with homeostatic model assessment insulin resistance (HOMA-IR), while AG positively correlated with HOMA-IR (R=0.6510, 0.005; R=0.8520, 0.000; R=0.5617, 0.013, respectively). Plasma UAG, TG and UAG/AG negatively correlated with serum LDL-C or hepatic triglycerides (TGs) (R=0.7733, P=0.001; R=0.6930, 0.003; R=0.6042, 0.008; R=0.7046, 0.002; R=0.6722, 0.004; R=0.5124, 0.020, respectively). Hypothalamic AG and GHSR-1a positively correlated with HOMA-IR or hepatic TGs (R=0.5116, 0.020; R=0.5220, 0.018; R=0.6074, 0.008; R=0.5127, 0.020, respectively).
It might be that decreased circulating UAG/AG, rather than UAG or AG alone, were involved in IR and liver lipid accumulation in NAFLD. Acylated ghrelin might induce IR and promote liver lipid accumulation via a central mechanism involved in the hypothalamus.
胃饥饿素是一种参与物质和能量代谢的脑肠肽。为证实胃饥饿素可能参与非酒精性脂肪性肝病（NAFLD）这一假说，建立了大鼠NAFLD模型并探讨胃饥饿素的变化。
将大鼠分为对照组和NAFLD组。NAFLD组大鼠给予高脂高胆固醇（HFHC）饮食8周。分别采用酶联免疫吸附测定（ELISA）、放射免疫分析（RIA）、逆转录聚合酶链反应（RT-PCR）和蛋白质免疫印迹法检测总胃饥饿素（TG）、酰化胃饥饿素（AG）、去酰化胃饥饿素（UAG）以及下丘脑AG及其受体生长激素促分泌素受体1a（GHSR-1a）的表达。
NAFLD组血浆UAG、TG以及UAG与AG的比值（UAG/AG）降低，而下丘脑AG和生长激素促分泌素受体-1a（GHSR-1a）的蛋白质和mRNA表达增加（P<0.01）。血浆UAG和UAG/AG与稳态模型评估胰岛素抵抗（HOMA-IR）呈负相关，而AG与HOMA-IR呈正相关（相关系数分别为R = 0.6510，P = 0.005；R = 0.8520，P = 0.000；R = 0.5617，P = 0.013）。血浆UAG、TG和UAG/AG与血清低密度脂蛋白胆固醇（LDL-C）或肝脏甘油三酯（TGs）呈负相关（相关系数分别为R = 0.7733，P = 0.001；R = 0.6930，P = 0.003；R = 0.6042，P = 0.008；R = 0.7046，P = 0.002；R = 0.6722，P = 0.004；R = 0.5124，P = 0.020）。下丘脑AG和GHSR-1a与HOMA-IR或肝脏TGs呈正相关（相关系数分别为R = 0.5116，P = 0.02；R = 0.5220，P = 0.018；R = 0.6074，P = 0.008；R = 0.5127，P = 0.02）。
可能是循环中UAG/AG降低，而非单独的UAG或AG降低，参与了NAFLD中的胰岛素抵抗和肝脏脂质蓄积。酰化胃饥饿素可能通过下丘脑相关的中枢机制诱导胰岛素抵抗并促进肝脏脂质蓄积。
