Research Article Details
| Article ID: | A25395 |
| PMID: | 21894008 |
| Source: | Dig Dis |
| Title: | Obesity and fatty liver are 'grease' for the machinery of hepatic fibrosis. |
| Abstract: | Nonalcoholic fatty liver disease (NAFLD) starts with hepatic steatosis, which can progress with inflammation to nonalcoholic steatohepatitis, and a subset of patients develop progressive fibrosis and ultimately cirrhosis. In the majority of cases, NAFLD is associated with (components of) the metabolic syndrome. Obesity, diabetes and hepatic steatosis are also independent risk factors for hepatic fibrosis in different chronic liver diseases. However, the question is whether it is actually nonalcoholic steatohepatitis and not 'simple' steatosis that promotes fibrosis progression based on hepatocellular injury. In this review, the concept will be put forward that (1) hepatic steatosis per se is profibrogenic, and (2) that in NAFLD development and progression of hepatic fibrosis is not simply determined by (the degree of) hepatic inflammation. In addition to the liver, this view is expanded to other organs affected by the metabolic syndrome, which affects hepatic injury and fibrosis also via extrahepatic pathophysiological alterations. In conclusion, fatty liver and the metabolic syndrome, respectively, have to be recognized as significant lubricants of hepatic fibrosis, and simple hepatic steatosis cannot be considered as benign. |
| DOI: | 10.1159/000329800 |
| 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 |
| 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 |