Research Article Details
| Article ID: | A11816 |
| PMID: | 30723896 |
| Source: | Lipids |
| Title: | Molecular Characterization of Microvesicular and Macrovesicular Steatosis Shows Widespread Differences in Metabolic Pathways. |
| Abstract: | Simple steatosis is the hallmark of nonalcoholic fatty liver disease, with lipid accumulating as either microvesicular or macrovesicular lipid droplets within hepatocytes. The present study used a combination of laser capture microdissection and RNAseq to characterize murine gene expression in nonsteatotic, microsteatotic, and macrosteatotic compartments collected from the same liver. The data indicate that microvesicular steatosis is intermediate to macrovesicular steatosis, showing a widespread and pronounced metabolic gene regulation of lipid export, gluconeogenesis, and de novo lipogenesis. Key enzymes, such as fatty acid synthase and fructose 1,6-bisphosphatase as well as apolipoprotein C-III, were identified to show clear expression differences between the compartments. Furthermore, increased expression of lipid particle formation genes provided a molecular description of the fusion of microsteatotic lipid compartments to produce macrosteatotic cells with a single enlarged lipid droplet. |
| DOI: | 10.1002/lipd.12121 |
| 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 |
| Diseases ID | DO ID | Disease Name | Definition | Class |
|---|
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D316 | S-adenosyl-L-methionine | Chemical drug | DB00118 | GNMT cofactor | Antiviral | Under clinical trials | Details |
| D142 | Fructose | Chemical drug | DB04173 | -- | Intravenous nutrition drug | Under clinical trials | Details |