Research Article Details
| Article ID: | A20642 |
| PMID: | 25838034 |
| Source: | Metabolism |
| Title: | Endoplasmic Reticulum Stress Response in Non-alcoholic Steatohepatitis: The Possible Role of Physical Exercise. |
| Abstract: | Sedentary lifestyle coupled with excessive consumption of high caloric food has been related to the epidemic increase of non-alcoholic fatty liver disease, which can progress from simple steatosis to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis and, eventually, may culminate in hepatocellular carcinoma. Although the precise mechanisms underlying the progression of NASH are not completely understood, endoplasmic reticulum (ER) dysfunction seems to play a key role in the process. Hepatic ER stress has been associated to hepatic steatosis, insulin resistance, inflammation, oxidative stress and hepatocyte death, contributing to liver dysfunction. Physical exercise seems to be the most effective preventive and therapeutic non-pharmacological strategy to mitigate several features related to NASH, possibly targeting most of the referred mechanisms associated with the pathophysiology of ER-related NASH. Nevertheless, little is known about the impact of physical exercise on NASH-related ER stress. In this review, we will discuss the ER stress associated to NASH conditions and highlight the possible benefits of physical exercise in the attenuation and/or reversion of NASH-related ER stress. |
| DOI: | 10.1016/j.metabol.2015.02.003 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S08 | Lifestyle measures | Lifestyle intervention; weight loss; diet adaptation; dietary interventions; lifestyle modifications; Exercise | -- | -- | Details |
| 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 |