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

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 (R(2)=0.6510, P=0.005; R(2)=0.8520, P=0.000; R(2)=0.5617, P=0.013, respectively). Plasma UAG, TG and UAG/AG negatively correlated with serum LDL-C or hepatic triglycerides (TGs) (R(2)=0.7733, P=0.001; R(2)=0.6930, P=0.003; R(2)=0.6042, P=0.008; R(2)=0.7046, P=0.002; R(2)=0.6722, P=0.004; R(2)=0.5124, P=0.020, respectively). Hypothalamic AG and GHSR-1a positively correlated with HOMA-IR or hepatic TGs (R(2)=0.5116, P=0.020; R(2)=0.5220, P=0.018; R(2)=0.6074, P=0.008; R(2)=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.