Research Article Details
| Article ID: | A06219 |
| PMID: | 32963741 |
| Source: | Iran J Basic Med Sci |
| Title: | The role of acylated ghrelin and unacylated ghrelin in the blood and hypothalamus and their interaction with nonalcoholic fatty liver disease. |
| Abstract: | Objectives: 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. |
| DOI: | 10.22038/ijbms.2020.45356.10555 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D160 | Growth Hormone | Biological drug | DB00052 | GHR ligand; PRLR ligand | -- | Under clinical trials | Details |
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D343 | Somatropin | Biological drug | DB00052 | GHR ligand; PRLR ligand | Hormone replacement drug | Under clinical trials | Details |