Research Article Details
| Article ID: | A08540 |
| PMID: | 32068022 |
| Source: | Gastroenterology |
| Title: | Metabolic Inflammation-A Role for Hepatic Inflammatory Pathways as Drivers of Comorbidities in Nonalcoholic Fatty Liver Disease? |
| Abstract: | Nonalcoholic fatty liver disease (NAFLD) is a global and growing health concern. Emerging evidence points toward metabolic inflammation as a key process in the fatty liver that contributes to multiorgan morbidity. Key extrahepatic comorbidities that are influenced by NAFLD are type 2 diabetes, cardiovascular disease, and impaired neurocognitive function. Importantly, the presence of nonalcoholic steatohepatitis and advanced hepatic fibrosis increase the risk for systemic comorbidity in NAFLD. Although the precise nature of the crosstalk between the liver and other organs has not yet been fully elucidated, there is emerging evidence that metabolic inflammation-in part, emanating from the fatty liver-is the engine that drives cellular dysfunction, cell death, and deleterious remodeling within various body tissues. This review describes several inflammatory pathways and mediators that have been implicated as links between NAFLD and type 2 diabetes, cardiovascular disease, and neurocognitive decline. |
| DOI: | 10.1053/j.gastro.2020.02.020 |
| 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 |
| 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 |