Iranian Journal of Basic Medical Sciences

Iranian Journal of Basic Medical Sciences

The role of acylated ghrelin and unacylated ghrelin in the blood and hypothalamus and their interaction with nonalcoholic fatty liver disease

Document Type : Original Article

Authors
Xia Liu 1
Yaoyao Guo 2
Zhaozhen Li 1
Yanling Gong 1
1 Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, China
2 Shandong Luoxin Pharmaceutical Group Stock Co., Ltd., Preparation Department, Linyi
10.22038/ijbms.2020.45356.10555
Abstract
Objective(s): 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.
Materials and Methods: 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.
Results: 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 (P<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 (R2=0.6510, P=0.005; R2=0.8520, P=0.000; R2=0.5617, P=0.013, respectively). Plasma UAG, TG and UAG/AG negatively correlated with serum LDL-C or hepatic triglycerides (TGs) (R2=0.7733, P=0.001; R2=0.6930, P=0.003; R2=0.6042, P=0.008; R2=0.7046, P=0.002; R2=0.6722, P=0.004; R2=0.5124, P=0.020, respectively). Hypothalamic AG and GHSR-1a positively correlated with HOMA-IR or hepatic TGs (R2=0.5116, P=0.020; R2=0.5220, P=0.018; R2=0.6074, P=0.008; R2=0.5127, P=0.020, respectively).
Conclusion: 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.
Keywords
Ghrelin Hypothalamus Insulin resistance Non
alcoholic fatty liver
disease Rat
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Iranian Journal of Basic Medical Sciences
Volume 23, Issue 9
September 2020
Pages 1191-1196