Research Article Details
| Article ID: | A48693 |
| PMID: | 31401190 |
| Source: | Biochimie |
| Title: | Apolipoprotein A-I improves hepatic autophagy through the AMPK pathway. |
| Abstract: | Dysfunction in lipid metabolism may result in a decrease in hepatic autophagy, which contributes to the pathogenesis of non-alcoholic steatohepatitis. ATP-binding cassette transporter A1 transports free cholesterol and phospholipids to apolipoprotein A-I (apoA-I) to form nascent high-density lipoprotein particles. Results from previous studies showed that the overexpression of apoA-I significantly reduced levels of hepatic lipids and endoplasmic reticulum stress by modifying lipid transport. Here, we investigated the effects of apoA-I overexpression on hepatic autophagy in cultured hepatocytes and mice. The overexpression of apoA-I in HepG2 cells resulted in an increase in the levels of autophagy as well as the phosphorylation of AMP-activated protein kinase α (AMPKα) and ULK1 and a decrease in the phosphorylation of mammalian target of rapamycin (mTOR). An AMPK inhibitor and siRNA eliminated this apoA-I effect. Consistently, apoA-I transgenic mice showed increased autophagy and AMPKα phosphorylation. These results suggest that apoA-I overexpression alleviates steatohepatitis by increasing hepatic autophagy through the AMPK-mTOR-ULK1 pathway. |
| DOI: | 10.1016/j.biochi.2019.08.001 |
| 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 |
| S13 | Anti-apoptosis | hepatocyte apoptosis; hepatic autophagy; apoptosis | Pan-caspase inhibitor | Emricasan | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class |
|---|
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D258 | Omega 3 PUFA | Chemical drug | DB11133 | PPARG ligand; PPARA activator | Hypolipidemic drug | Under clinical trials | Details |
| D612 | Rapamycin | Miscellany | -- | Immunosuppressants; Methylmalonyl CoA mutase stimulants; MTOR protein inhibitors; T lymphocyte inhibitors | -- | Under investigation | Details |
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D589 | Minor allele-specific small interfering RNA | Miscellany | -- | PNPLA3-rs738409 (I148M) variant inhibitor | -- | Under investigation | Details |
| D125 | Epanova | Chemical drug | DB11133 | PPARG ligand; PPARA activator | Enhance lipid metabolism | Under clinical trials | Details |