Research Article Details
| Article ID: | A15560 |
| PMID: | 28843826 |
| Source: | Eur J Pharmacol |
| Title: | Zoledronic acid, an FPPS inhibitor, ameliorates liver steatosis through inhibiting hepatic de novo lipogenesis. |
| Abstract: | Currently, there is no standard therapy for non-alcoholic fatty liver disease (NAFLD), and statins have been developed as a first-line pharmaceutical therapeutic option for NAFLD-associated dyslipidemia. However, prolonged statins therapy has side effects, as statins inhibit HMG-CoA reductase, an enzyme at the very beginning of the mevalonate pathway. Here, we found that zoledronic acid (ZA), an inhibitor of farnesyl diphosphate synthase in the downstream mevalonate pathway, could attenuate hepatic lipid accumulation and improve liver injury in both high-fat diet-induced C57BL/6J mice and ob/ob mice. Moreover, the hepatic lipid metabolism was largely inhibited after ZA administration in high-fat diet-induced obese mice. Mechanically, ZA inhibited SREBP-1c-mediated de novo lipogenesis through suppressing RhoA activation via decreasing farnesyl diphosphate and geranylgeranyl diphosphate levels. In conclusion, our data provide a novel application of ZA in improving hepatic steatosis. |
| DOI: | 10.1016/j.ejphar.2017.08.010 |
| 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 |
| 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 | |
|---|---|---|---|---|---|---|---|
| T10 | Caspase-1 | CASP1 | inhibitor | Enzyme | P29466 | CASP1_HUMAN | Details |
| T18 | Acetyl-CoA carboxylase 1 | ACACA | inhibitor | Enzyme | Q13085 | ACACA_HUMAN | Details |
| T15 | 3-hydroxy-3-methylglutaryl-coenzyme A reductase | HMGCR | inhibitor | Enzyme | P04035 | HMDH_HUMAN | Details |