Research Article Details
| Article ID: | A06491 |
| PMID: | 32856978 |
| Source: | J Med Food |
| Title: | Fisetin Alleviates Hepatic and Adipocyte Fibrosis and Insulin Resistance in Diet-Induced Obese Mice. |
| Abstract: | The present study aimed to investigate the protective role of the flavonoid fisetin (FI) on inflammation-mediated metabolic diseases, especially tissue fibrosis and insulin resistance (IR) in high-fat diet (HFD)-induced obese mice. C57BL/6J mice were fed with normal-fat diet, HFD (40 kcal% fat), or HFD +0.02% (w/w) FI for 16 weeks. Dietary FI supplementation improved hepatic steatosis by restricting lipogenesis, while promoting lipolysis in the liver. FI also prevented adiposity via an increase in the expression of genes involved in FA oxidation and a decrease in the expression of genes involved in lipogenesis in white adipose tissue. In addition, FI increased brown adipose tissue (BAT) and skeletal muscle weights, thermogenic gene mRNA expression in BAT, and tricarboxylic acid cycle-related gene expression in skeletal muscle, which may be linked to the prevention of nonalcoholic fatty liver disease as well as adiposity. Moreover, FI supplementation decreased excessive reactive oxygen species production by increasing paraoxonase activity, adipokine dysregulation, proinflammatory cytokine production, and extracellular matrix amassment in the liver. FI supplementation ameliorated IR, in part, by normalizing pancreatic islet dysfunction, and it declined hepatic gluconeogenesis and proinflammatory responses. Taken together, the present findings indicate that FI can protect against HFD-induced inflammation-mediated disorders, including fibrosis and IR. |
| DOI: | 10.1089/jmf.2019.4619 |
| 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 |
| S03 | Anti-fibrosis | fibrosis | Angiotensin Receptor Blocker (ARB); CCR2/CCR5 antagonist; Thyroid receptor β agonist; PEGylated human FGF21 analogue; Monoclonal antibody to lysyl oxidase-like 2 (LOXL2); Galectin-3 inhibitor; FGF19 variant | Losartan; Cenicriviroc; VK-2809; MGL-3196; Pegbelfermin; Simtuzumab; GR-MD-02; NGM282 | 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 |
| 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 |