Research Article Details
| Article ID: | A01246 |
| PMID: | 34815180 |
| Source: | Trends Mol Med |
| Title: | Linking liver metabolic and vascular disease via bile acid signaling. |
| Abstract: | Non-alcoholic fatty liver disease (NAFLD) is a metabolic disorder affecting over one quarter of the global population. Liver fat accumulation in NAFLD is promoted by increased de novo lipogenesis leading to the development of a proatherosclerotic lipid profile and atherosclerotic cardiovascular disease (CVD). The CVD component of NAFLD is the main determinant of patient outcome. The farnesoid X receptor (FXR) and the G protein bile acid-activated receptor 1 (GPBAR1) are bile acid-activated receptors that modulate inflammation and lipid and glucose metabolism in the liver and CV system, and are thus potential therapeutic targets. We review bile acid signaling in liver, metabolic tissues, and the CV system, and we propose the development of dual FXR/GPBAR1 ligands, intestine-restricted FXR ligands, or statin combinations to limit side effects and effectively manage the liver and CV components of NAFLD. |
| DOI: | 10.1016/j.molmed.2021.10.005 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| 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 |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name | |
|---|---|---|---|---|---|---|---|
| T17 | Farnesoid X-activated receptor | NR1H4 | agonist | Nuclear hormone receptor | Q96RI1 | NR1H4_HUMAN | Details |
| T18 | Acetyl-CoA carboxylase 1 | ACACA | inhibitor | Enzyme | Q13085 | ACACA_HUMAN | Details |
| T07 | Bile acid receptor | NR1H4 | agonist | Nuclear hormone receptor | Q96RI1 | NR1H4_HUMAN | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class |
|---|
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress |
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