Research Article Details
| Article ID: | A08988 |
| PMID: | 31914377 |
| Source: | Cell Metab |
| Title: | Leveraging Human Genetics to Identify Potential New Treatments for Fatty Liver Disease. |
| Abstract: | Fatty liver disease (FLD), including its more severe pathologies, namely steatohepatitis, hepatocarcinoma, and cirrhosis, is the most common cause of chronic liver disease worldwide and is projected to become the leading cause of hepatocellular carcinoma and end-stage liver disease. FLD is heterogeneous with multiple etiologies and diverse histological phenotypes, so therapies will ultimately need to be individualized for relevant targets. Inherited factors contribute to FLD, and most of the genetic variation influencing liver disease development and progression is derived from genes involved in lipid biology, including PNPLA3, TM6SF2, GCKR, MBOAT7, and HSD17B13. From this point of view, we focus in this perspective on how human molecular genetics of FLD have highlighted defects in hepatic lipid handling as a major common mechanism of its pathology and how this insight could be leveraged to treat and prevent its more serious complications. |
| DOI: | 10.1016/j.cmet.2019.12.002 |
| 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 |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
|---|
| Diseases ID | DO ID | Disease Name | Definition | Class |
|---|
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D248 | Obeticholic Acid | Chemical drug | DB05990 | NR1H4 activator; NR1H4 agonist; FXR agonist | Enhance lipid metabolism | Approval rejected | Details |
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |