Research Article Details
| Article ID: | A14742 |
| PMID: | 29263118 |
| Source: | Physiol Rep |
| Title: | In vitro cellular models of human hepatic fatty acid metabolism: differences between Huh7 and HepG2 cell lines in human and fetal bovine culturing serum. |
| Abstract: | Human primary hepatocytes are the gold standard for investigating lipid metabolism in nonalcoholic fatty liver disease (NAFLD); however, due to limitations including availability and donor variability, the hepatoma cell lines Huh7 and HepG2 are commonly used. Culturing these cell lines in human serum (HS) has been reported to improve functionality; however, direct comparison of fatty acid (FA) metabolism in response to culturing in HS is lacking. The aim of this study was to compare FA metabolism between HepG2 and Huh7 cells in response to culturing in different sera. Both HepG2 and Huh7 cells were grown in media containing 11 mmol/L glucose and either 2% HS or 10% fetal bovine serum. After 3 days, insulin and insulin-like growth factor-1 signaling were measured. At 7 days, intracellular triacylglycerol (TAG) and media 3-hydroxybutyrate, TAG and apolipoprotein B were measured, as was the FA composition of intracellular TAG and phospholipids. Both cell lines demonstrated higher levels of polyunsaturated fatty acid content, increased insulin sensitivity, higher media TAG levels and increased FA oxidation when cultured in HS Notably, independent of serum type, Huh7 cells had higher intracellular TAG compared to HepG2 cells, which was in part attributable to a higher de novo lipogenesis. Our data demonstrate that intrahepatocellular FA metabolism is different between cell lines and influenced by culturing sera. As a result, when developing a physiologically-relevant model of FA metabolism that could be developed for the study of NAFLD, consideration of both parameters is required. |
| DOI: | 10.14814/phy2.13532 |
| 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 |
|---|
| 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 |
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D080 | Citrulline | Chemical drug | DB00155 | -- | -- | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D125 | Epanova | Chemical drug | DB11133 | PPARG ligand; PPARA activator | Enhance lipid metabolism | Under clinical trials | Details |
| D094 | Cysteamine | Chemical drug | DB00847 | GSS stimulant | Renal drug | Under clinical trials | Details |
| D095 | Cysteamine bitartrate | Chemical drug | DB00847 | -- | -- | Under clinical trials | Details |