Research Article Details
| Article ID: | A47873 |
| PMID: | 30393432 |
| Source: | J Toxicol Pathol |
| Title: | Hepatic lesions induced by feeding Western diets to Zucker fatty rats, an insulin-resistant model. |
| Abstract: | Metabolic diseases including nonalcoholic steatohepatitis develop due to various environmental factors. In particular, the westernization of food is closely related to the development of these diseases. In this study, we investigated pathophysiological changes in the livers of Zucker fatty (ZF) rats induced by feeding Western diets. Male ZF rats were fed a sucrose/fat/cholesterol-enriched diet (Western diet, WD) or standard diet (SD) for 18 weeks, from 7 to 25 weeks of age. Body weight, food intake, and biochemical parameters were periodically measured, histopathological analyses were performed at 25 weeks, and mRNA expression in the liver was determined. ZF rats fed the WD (ZF-WD rats) developed obesity, hyperinsulinemia, hyperglycemia, and hyperlipidemia, and their alanine aminotransferase and aspartate aminotransferase levels increased compared with those of ZF rats fed the SD (ZF-SD rats). Hepatic lesions including fibrosis and necrosis were observed in the ZF-WD rats at 25 weeks; however, fibrosis and necrosis were not observed in the ZF-SD rats. Oxidative stress markers also increased in the livers of ZF-WD rats. Hepatic mRNA expression related to inflammation and fibrosis increased in the ZF-WD rats; however, mRNA expression related to lipid synthesis decreased. Microsomal triglyceride transfer protein mRNA levels in the ZF-WD rats also decreased. In Zucker lean rats fed the WD, similar changes were observed in the liver; however, the hepatic changes were not serious compared with ZF-WD rats. In conclusion, hepatic lesions, such as inflammation, fibrosis, and necrosis, were observed in the ZF-WD rats. The sucrose/fat/cholesterol-enriched diet induced significant lipotoxicity in the livers of animals in this insulin-resistant model. |
| DOI: | 10.1293/tox.2018-0016 |
| 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 |
| S04 | Anti-oxidative stress | oxidative stress | α-tocopherol: antioxidant | Vitamin E | Details |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
|---|
| 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 |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| 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 |
| D080 | Citrulline | Chemical drug | DB00155 | -- | -- | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | 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 |