Research Article Details
| Article ID: | A11580 |
| PMID: | 30832407 |
| Source: | Nutrients |
| Title: | Dietary Polyphenols Protect Against Oleic Acid-Induced Steatosis in an in Vitro Model of NAFLD by Modulating Lipid Metabolism and Improving Mitochondrial Function. |
| Abstract: | In this study, we aimed to determine the relative effectiveness of common dietary polyphenols or the isoquinoline alkaloid berberine in protecting against molecular mechanisms underlying non-alcoholic fatty liver disease (NAFLD) involving changes to cellular lipid metabolism and bioenergetics. In a model of steatosis using HepG2 hepatocytes, exposure of the cells to 1.5 mM oleic acid (OA) for 24 h caused steatosis and distorted cell morphology, induced the expression of mRNA for enzymes that are involved in lipogenesis and fatty acid oxidation (FAS and CPT1A), and impaired indices of aerobic energy metabolism (PPARγ mRNA expression, mitochondrial membrane potential (MMP), and galactose-supported ATP production). Co-treatment with 10 µM of selected polyphenols all strongly protected against the steatosis and changes in cell morphology. All polyphenols, except cyanidin, inhibited the effects on FAS and PPARγ and further increased CPT1A1 expression, suggesting a shift toward increased β-oxidation. Resveratrol, quercetin, catechin, and cyanidin, however not kuromanin or berberine, ameliorated the decreases in MMP and galactose-derived ATP. Berberine was unique in worsening the decrease in galactose-derived ATP. In further investigations of the mechanisms involved, resveratrol, catechin, and berberine increased SIRT1 enzyme activity and p-AMPKαThr172 protein, which are involved in mitochondrial biogenesis. In conclusion, selected polyphenols all protected against steatosis with similar effectiveness, however through different mechanisms that increased aerobic lipid metabolism and mitochondrial function. |
| DOI: | 10.3390/nu11030541 |
| 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 | |
|---|---|---|---|---|---|---|---|
| T01 | 5'-AMP-activated protein kinase subunit beta-1 | PRKAB1 | activator | Kinase | Q9Y478 | AAKB1_HUMAN | Details |
| T10 | Caspase-1 | CASP1 | inhibitor | Enzyme | P29466 | CASP1_HUMAN | Details |
| T26 | Thyroid hormone receptor beta | THRB | agonist | Nuclear hormone receptor | P10828 | THB_HUMAN | Details |
| T20 | Fatty acid synthase | FASN | inhibitor | Enzyme | P49327 | FAS_HUMAN | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class |
|---|
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D293 | Quercetin | Supplement | DB04216 | AHR; EIF3F; SF3B3; NR1I2 activator | -- | Under clinical trials | Details |
| D201 | L-Carnitine | Supplement | DB00583 | SLC22A4; SLC22A5; CRAT; MPO | -- | Under clinical trials | Details |
| D301 | Resveratrol | Chemical drug | DB02709 | ALOX15; ALOX5; AHR; NR1I2; NR1I3 | Anticancer agent | Under clinical trials | Details |
| D029 | Berberine | Chemical drug | DB04115 | AMPK activator | Improve insulin resistance | Under clinical trials | Details |
| D062 | Carnitine complex | Supplement | DB00583 | SLC22A4; SLC22A5; CRAT; MPO | -- | Under clinical trials | Details |