Research Article Details
| Article ID: | A19208 |
| PMID: | 26703097 |
| Source: | Trends Endocrinol Metab |
| Title: | The Role of Cholesterol in the Pathogenesis of NASH. |
| Abstract: | Lipotoxicity drives the development of progressive hepatic inflammation and fibrosis in a subgroup of patients with nonalcoholic fatty liver disease (NAFLD), causing nonalcoholic steatohepatitis (NASH) and even progression to cirrhosis and hepatocellular carcinoma (HCC). While the underlying molecular mechanisms responsible for the development of inflammation and fibrosis that characterize progressive NASH remain unclear, emerging evidence now suggests that hepatic free cholesterol (FC) is a major lipotoxic molecule critical in the development of experimental and human NASH. In this review, we examine the effects of excess FC in hepatocytes, Kupffer cells (KCs), and hepatic stellate cells (HSCs), and the subcellular mechanisms by which excess FC can induce cellular toxicity or proinflammatory and profibrotic effects in these cells. |
| DOI: | 10.1016/j.tem.2015.11.008 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S02 | Enhance lipid metabolism | triglyceride-lowering; lipid tolerance; lipid metabolism | 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitor; Decreases intestinal cholesterol absorption; FXR agonist; ACC inhibitor; FAS inhibitor; DGAT2 inhibitor; SCD-1 inhibitor | Atorvastatin; Ezetimibe; Obeticholic Acid; GS-9674; GS-0976; TVB-2640; IONIS-DGAT2rx; Aramchol; | 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 |
|---|