Research Article Details
| Article ID: | A14393 |
| PMID: | 29429367 |
| Source: | Arch Physiol Biochem |
| Title: | Obestatin protects and reverses nonalcoholic fatty liver disease and its associated insulin resistance in rats via inhibition of food intake, enhancing hepatic adiponectin signaling, and blocking ghrelin acylation. |
| Abstract: | This study investigated the ameliorative and protective effects of long-term obestatin administration (80 nmol/kg/ intraperitoneal injection (i.p.)) on the pathogenesis of high-fat diet (HFD) induced nonalcoholic fatty liver disease (NAFLD) in rats. Rats (n = 8/group) were divided as control, NAFLD, NAFLD + Simvastatin, NAFLD + obestatin, NAFLD then obestatin, and obestatin then NAFLD. Obestatin co -or post-therapy significantly reduced hepatomegaly and reversed hyperlipidemia, hepatic lipid accumulation, and insulin resistance (IR). Mechanistically obestatin treatments in these rats significantly prevented the increases in final body weights and food intake. Concomitantly, it enhanced circulatory adiponectin levels and hepatic signaling as evident by elevated hepatic protein levels of adiponectin receptors (adipoRII), carnitine palmitoyltransferase-1 (CPT-1), peroxisome proliferator-activated receptor- α (PPAR-α), and phosphor-AMPK (p-AMPK). In addition, obestatin enhanced total circulatory ghrelin levels and significantly increased deacylated ghrelin to acylated ghrelin (DAG/AG) ratio. These data suggest that obestatin reverses and protects against development or progression of NAFLD directly by modulating ghrelin and adiponectin signaling or indirectly by lowering food intake. |
| DOI: | 10.1080/13813455.2018.1437638 |
| 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 |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name | |
|---|---|---|---|---|---|---|---|
| T08 | Tumor necrosis factor | TNF | inhibitor | Cytokine | P01375 | TNFA_HUMAN | Details |
| T01 | 5'-AMP-activated protein kinase subunit beta-1 | PRKAB1 | activator | Kinase | Q9Y478 | AAKB1_HUMAN | Details |
| T18 | Acetyl-CoA carboxylase 1 | ACACA | inhibitor | Enzyme | Q13085 | ACACA_HUMAN | 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 | |
|---|---|---|---|---|---|---|---|
| D201 | L-Carnitine | Supplement | DB00583 | SLC22A4; SLC22A5; CRAT; MPO | -- | Under clinical trials | Details |
| D579 | Emfilermin | Miscellany | -- | adipocytes | Enhance lipid metabolism | Under investigation | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D062 | Carnitine complex | Supplement | DB00583 | SLC22A4; SLC22A5; CRAT; MPO | -- | Under clinical trials | Details |