Research Article Details
| Article ID: | A07814 |
| PMID: | 32348835 |
| Source: | Life Sci |
| Title: | Exenatide ameliorates experimental non-alcoholic fatty liver in rats via suppression of toll-like receptor 4/NFκB signaling: Comparison to metformin. |
| Abstract: | AIMS: Non-alcoholic fatty liver disease (NAFLD) is a common liver disease. This study aimed to evaluate the role of exenatide compared with metformin in halting the progression of fatty liver stimulated by a high-fat diet (HiFD) in rats. MAIN METHODS: Thirty male Wistar rats were allocated into 6 groups, 5 rats per each group. Group I: maintained on normal diet (normal group) for fourteen weeks. The other five groups were kept on HiFD throughout the experiment, HiFD was administered beside pharmacological treatments/or vehicle. Group II: (NAFLD control group), group III: received metformin (60 mg/kg/day, P.O.), group IV-VI: received exenatide (10, 20, and 40 μg/kg/day, S.C.) respectively for 7 weeks. At the end of the therapeutic period, fasting blood glucose was determined, and body weight was registered. Rats were sacrificed, and blood samples were taken to measure serum insulin, lipids, and liver enzymes. The liver index and homeostasis model of insulin resistance (HOMA-IR) index were calculated. Further, livers were dissected for histopathological examination and Western blot analysis. KEY FINDINGS: NAFLD control group showed hyperglycemia, hyperinsulinemia, increased liver enzymes, hypertriglyceridemia, elevated hepatic lipid peroxides, and inflammatory mediators (interlukin 6, nuclear factor-κB, tumor necrosis factor-α and Toll-like receptor4) in addition to hepatic fatty degeneration. In a dose-dependent manner, exenatide significantly improved most of the above mentioned markers in comparsion with NAFLD at P≤0.05. SIGNIFICANCE: The current results suggest that exenatide is equivalent to metformin in controlling insulin resistance, body weight gain, improving liver function, suppressing inflammation, and attenuating NAFLD progression in male rats. |
| DOI: | 10.1016/j.lfs.2020.117725 |
| 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 |
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | Details |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name | |
|---|---|---|---|---|---|---|---|
| T08 | Tumor necrosis factor | TNF | inhibitor | Cytokine | P01375 | TNFA_HUMAN | Details |
| T09 | Toll-like receptor 4 | TLR4 | antagonist | Membrane receptor | O00206 | TLR4_HUMAN | Details |
| T10 | Caspase-1 | CASP1 | inhibitor | Enzyme | P29466 | CASP1_HUMAN | Details |
| T20 | Fatty acid synthase | FASN | inhibitor | Enzyme | P49327 | FAS_HUMAN | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I13 | 3146 | Lipid metabolism disorder | An inherited metabolic disorder that involves the creation and degradation of lipids. http://en.wikipedia.org/wiki/Lipid_metabolism | disease of metabolism/ inherited metabolic disorder | Details |
| 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 | |
|---|---|---|---|---|---|---|---|
| D129 | Exenatide | Biological drug | DB01276 | GLP1R activator; GLP1R agonist | Improve insulin resistance | Under clinical trials | Details |
| D225 | Metformin | Chemical drug | DB00331 | PRKAB1 inducer activator; ETEDH inhibitor; GPD1 inhibitor | Improve insulin resistance | Under clinical trials | Details |
| D579 | Emfilermin | Miscellany | -- | adipocytes | Enhance lipid metabolism | Under investigation | 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 |
| D248 | Obeticholic Acid | Chemical drug | DB05990 | NR1H4 activator; NR1H4 agonist; FXR agonist | Enhance lipid metabolism | Approval rejected | Details |
| D316 | S-adenosyl-L-methionine | Chemical drug | DB00118 | GNMT cofactor | Antiviral | Under clinical trials | Details |
| D157 | Glucophage | Chemical drug | DB00331 | -- | -- | Under clinical trials | Details |
| D094 | Cysteamine | Chemical drug | DB00847 | GSS stimulant | Renal drug | Under clinical trials | Details |
| D095 | Cysteamine bitartrate | Chemical drug | DB00847 | -- | -- | Under clinical trials | Details |