Research Article Details
| Article ID: | A10813 |
| PMID: | 31176759 |
| Source: | Mol Cell Endocrinol |
| Title: | Adiponectin is required for pioglitazone-induced improvements in hepatic steatosis in mice fed a high-fat diet. |
| Abstract: | Pioglitazone has been used for the treatment of nonalcoholic fatty liver disease (NAFLD) related to diabetes. The role of adiponectin in pioglitazone-induced improvements in NAFLD was studied by using wild-type (adipoWT) and adiponectin knockout (adipoKO) mice. High-fat diet fed mice were insulin resistant, glucose intolerant and had increased hepatic lipid accumulation as evidenced by increased NAFLD activity score. Despite pioglitazone has improved insulin resistance in both genotypes, hepatic steatosis was only improved in adipoWT obese mice. Amelioration of NAFLD in adipoWT mice promoted by pioglitazone was associated with up-regulation of Pparg, Fgf21 and down-regulation of Pepck liver expression. On the other hand, resistance to pioglitazone treatment in adipoKO mice was associated with increased expression of miR-192 and Hsl, which was not followed by increased fatty acid oxidation. In conclusion, our data provides evidence that increased adiponectin production by pioglitazone is necessary for its beneficial action on NAFLD. |
| DOI: | 10.1016/j.mce.2019.110480 |
| 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 | |
|---|---|---|---|---|---|---|---|
| T10 | Caspase-1 | CASP1 | inhibitor | Enzyme | P29466 | CASP1_HUMAN | Details |
| T18 | Acetyl-CoA carboxylase 1 | ACACA | inhibitor | Enzyme | Q13085 | ACACA_HUMAN | Details |
| T28 | Fibroblast growth factor 21 | FGF21 | analogue | Secreted | Q9NSA1 | FGF21_HUMAN | Details |
| T05 | Peroxisome proliferator-activated receptor gamma | PPARG | agonist | Nuclear hormone receptor | P37231 | PPARG_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 |
| I14 | 9970 | Obesity | An overnutrition that is characterized by excess body fat, traditionally defined as an elevated ratio of weight to height (specifically 30 kilograms per meter squared), has_material_basis_in a multifactorial etiology related to excess nutrition intake, decreased caloric utilization, and genetic susceptibility, and possibly medications and certain disorders of metabolism, endocrine function, and mental illness. https://en.wikipedia.org/wiki/Obesity | disease of metabolism/acquired metabolic disease/ nutrition disease/overnutrition | Details |