Research Article Details
| Article ID: | A46294 |
| PMID: | 19726979 |
| Source: | Curr Opin Clin Nutr Metab Care |
| Title: | Nutritional related liver disease: targeting the endoplasmic reticulum stress. |
| Abstract: | PURPOSE OF REVIEW: Nutritional hepatic disorders are spreading worldwide associated to obesity and type 2 diabetes. The underlying mechanisms leading to the development of hepatic steatosis and its complications are not fully understood. The endoplasmic reticulum (ER) stress response has recently been proposed to play a crucial role in the setting of these pathologies. This review will evaluate the late discoveries highlighting ER stress as a major actor in the development of nutritional liver diseases. RECENT FINDINGS: Activation of ER stress has been reported in the fatty liver of obese rodents and obese individuals. The mechanisms by which ER stress leads to the development of hepatic steatosis have been recently documented. ER stress has been shown to directly activate the lipogenic transcription factor SREBP-1c (sterol regulatory element binding protein-1c) conducting to an induction of the lipogenic pathway. ER stress activation is also associated with impaired VLDL (very low density lipoprotein) secretion. ER stress could also have a role in hepatic steatosis progression by triggering inflammation and fibrosis. In rodents, therapies aiming to reduce ER stress have fully demonstrated their efficiency in the treatment of hepatic steatosis. SUMMARY: ER stress has been recently involved in the development of hepatic steatosis. Thus, ER stress could represent in the future an eligible therapeutic target for the treatment of nonalcoholic fatty liver disease. However, as ER stress is a fundamental mechanism involved in cell survival, any modification of this pathway must be carefully assessed. |
| DOI: | 10.1097/MCO.0b013e32833189db |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| 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 |
| 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 |
|---|