Research Article Details
| Article ID: | A26813 |
| PMID: | 19731869 |
| Source: | Vnitr Lek |
| Title: | [Metabolic syndrome and the liver (NAFLD/NASH)]. |
| Abstract: | Metabolic syndrome (MS) is one of the most prevalent disease states in the so-called developed countries and is closely associated with the incidence of cardiovascular as well as other diseases. Predominant sign is the abdominal type of obesity with increased visceral fat mass and the associated insulin resistance. Glucose metabolism disorder, dyslipidemia and arterial hypertension are other important attributes. Metabolic syndrome is also closely associated with the liver steatosis, mostly benign and reversible liver disease. Nevertheless, uncomplicated steatosis may, under certain conditions, progress to inflammation and the disease may, through the stage of NASH (nonalcoholic steatohepatitis) and liver fibrosis, result in liver cirrhosis and hepatocellular carcinoma. Anglo-Saxon literature uses the term NAFLD (non-alcoholic fatty liver disease) to refer to these various stages ofthe liver disease (uncomplicated liver steatosis, steatohepatitis, fibrosis and cirrhosis). While simple steatosis is not dangerous for the patient, NASH is the sign of developing cirrhosis. Etiopathogenesis of NASH features identical characteristics as etiopathogenesis of insulin resistance and metabolic syndrome. Even though liver biopsy remains the gold standard in the diagnosis, new diagnostic approaches are emerging that could be useful in distinguishing simple steatosis from NASH. Therapy includes lifestyle changes, insulin resistance-reducing medication (also useful in the treatment of type 2 diabetes) with a range of other agents under development. In the meantime, randomized double-blind placebo-controlled studies with histological proof of the results are still lacking. A range of unresolved issues remains with regards to etiopathogenesis as well as diagnosis and treatment of NAFLD and NASH. |
| DOI: |
| 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 | |
|---|---|---|---|---|---|
| I13 | 3146 | Lipid metabolism disorder | An inherited metabolic disorder that involves the creation and degradation of lipids. http://en.wikipedia.org/wiki/Lipid_metabolism | disease of metabolism/ inherited metabolic disorder | Details |
| I12 | 10763 | Hypertension | An artery disease characterized by chronic elevated blood pressure in the arteries. https://en.wikipedia.org/wiki/Hypertension, https://www.ncbi.nlm.nih.gov/pubmed/24352797 | disease of anatomical entity/ cardiovascular system disease/vascular disease/ artery disease | Details |
| 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 | |
|---|---|---|---|---|---|---|---|
| D579 | Emfilermin | Miscellany | -- | adipocytes | Enhance lipid metabolism | Under investigation | Details |
| D010 | Amoxicillin | Chemical drug | DB01060 | -- | -- | 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 |