Research Article Details
| Article ID: | A25161 |
| PMID: | 22122481 |
| Source: | Curr Pharm Biotechnol |
| Title: | Non-alcoholic steatohepatitis: new insights from OMICS studies. |
| Abstract: | Non-alcoholic fatty liver disease (NAFLD) is the most common liver pathology characterized by fat accumulation in a context of metabolic syndrome or insulin resistance. It can be associated with obesity, diabetes, hyperinsulinemia, dyslipidemia as well as hypertension. NAFLD consists of a large spectrum of hepatic lesions including benign steatosis, non-alcoholic steatohepatitis (NASH), cirrhosis or hepatocellular carcinoma. Upon chronic stress, NASH would occur via at least "two-hits" process involving modulation of a high number of genes and proteins. Firstly, the accumulation of fat, either due to the increased inflow of free fatty acids or de novo lipogenesis, leads to steatosis. Secondly, when adaptive mechanisms for stress tolerance are overwhelmed, lipotoxicity and chronic inflammation trigger major hepatic damages, mainly via oxidative and inflammatory stress, lipid peroxidation and cell death. As a consequence, all these processes concur to favor steatohepatitis, fibrosis and cancer. Recently, the elucidation of physiopathological signaling cascades controlling NAFLD and NASH benefited from large-scale studies, namely the omics, such as transcriptomics, genomics, proteomics, and lipidomics. The advent of lipidomics would allow shedding light upon the respective roles of triglyceride and fatty acid metabolites in the lipotoxic liver injury hypothesis for the pathogenesis of NASH. In this review, the contribution of the omics to the understanding of the molecular basis of NASH is discussed that could offer perspectives for novel biomarkers discovery. |
| DOI: | 10.2174/138920112799857558 |
| 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 |
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | Details |
| S07 | Anti-lipogenesis | de novo lipogenesis; de novo lipogenesis; DNL; anti-lipogenic mechanisms; adipogenesis; anti-obesity | stearoyl-CoA desaturase 1 (SCD-1); Acetyl-coenzyme carboxylase; acyl-CoA carboxylase inhibitor (ACC inhibitor); stearoyl Coenzyme A desaturase inhibitor (SCD inhibitor); THR-beta selective agonist; DGAT2 inhibitor; FASN inhibitor | Aramchol; Firsocostat (GS-0976); VK-2809; ION 224 | Details |
| 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 |