Research Article Details
| Article ID: | A13147 |
| PMID: | 30115876 |
| Source: | Molecules |
| Title: | Hepatoprotective Effects of MHY3200 on High-Fat, Diet-Induced, Non-Alcoholic Fatty Liver Disease in Rats. |
| Abstract: | This study investigated the effects of 2-(4-(5-chlorobenzo[d]thiazol-2-yl)phenoxy)-2,2-difluoroacetic acid (MHY3200) on high-fat diet (HFD)-induced hepatic lipid accumulation and inflammation. The measurement of peroxisome proliferator-activated receptor (PPAR)α activity by using a luciferase assay indicated that MHY3200 was more potent than a known PPARα agonist, WY14643, in AC2F cells. Six-month-old male SD rats were fed chow or HFD for 1 month, and after, with or without added MHY3200 (1 or 2 mg/kg/day) for 4 weeks. The oral administration of MHY3200 caused a significant decrease in serum triglyceride (TG), glucose, alanine aminotransferase, and insulin, as well as a slight decrease in the level of free fatty acid and aspartate transaminase. No weight gain was detected when compared with HFD rats, and hepatic TG content was also attenuated by the administration of MHY3200. Furthermore, phosphorylation of the ER stress marker, inositol-requiring kinase 1 and its downstream gene, c-Jun N-terminal kinase, in addition to serine phosphorylation of insulin receptor substrate 1 were suppressed by MHY3200. Consistent with these results, MHY3200 administration reduced the levels of activation of protein-1, cyclooxygenase-2, and inducible nitric oxide synthase. Our results suggested that MHY3200 ameliorated HFD-induced hepatic lipid accumulation and inflammation, and improved insulin resistance through PPARα activation. |
| DOI: | 10.3390/molecules23082057 |
| 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 |
| S02 | Enhance lipid metabolism | triglyceride-lowering; lipid tolerance; lipid metabolism | 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitor; Decreases intestinal cholesterol absorption; FXR agonist; ACC inhibitor; FAS inhibitor; DGAT2 inhibitor; SCD-1 inhibitor | Atorvastatin; Ezetimibe; Obeticholic Acid; GS-9674; GS-0976; TVB-2640; IONIS-DGAT2rx; Aramchol; | 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 | |
|---|---|---|---|---|---|---|---|
| D579 | Emfilermin | Miscellany | -- | adipocytes | Enhance lipid metabolism | Under investigation | Details |
| D199 | L-alanine | Chemical drug | DB00160 | KYNU | -- | Failed in 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 |
| D316 | S-adenosyl-L-methionine | Chemical drug | DB00118 | GNMT cofactor | Antiviral | 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 |