Research Article Details
| Article ID: | A14020 |
| PMID: | 29631603 |
| Source: | Lipids Health Dis |
| Title: | Heat shock protein 70 promotes lipogenesis in HepG2 cells. |
| Abstract: | BACKGROUND: The increasing prevalence of non-alcoholic fatty liver disease (NAFLD) has followed the international rise in obesity rates. Multiple mechanisms are involved in NAFLD, including endoplasmic reticulum stress and oxidative stress. Heat shock protein 70 (HSP70), which is abundant in most organisms, is sensitive to stress. However, the role of HSP70 in NAFLD has not been investigated. Here, we investigated the possible role of HSP70 in lipid synthesis. METHODS: C57BL/6 mice were fed a high-fat diet, and HepG2 cells were treated with 0.5 mM palmitic acid (PA). HSP70 expression was detected by qPCR, Western blot and immunohistochemistry. Total cholesterol (TC) and triglyceride (TG) levels were detected by enzyme-linked immunosorbent assay (ELISA). After Hsp70 overexpression and knockdown, TC and TG levels and FAS, SCD, and ACC expression were detected. RESULTS: HSP70 expression was significantly increased in the livers of obese mice. In vitro, HSP70 expression was markedly induced by PA in HepG2 cells. Notably, HSP70 overexpression in HepG2 cells enhanced TC and TG synthesis, in parallel with the upregulation of lipogenic genes, including FAS, SCD and ACC. By contrast, HSP70 knockdown decreased the levels of cellular lipids and the expression of FAS, SCD, and ACC in HepG2 cells. Together, our results suggest that HSP70 may promote lipogenesis in HepG2 cells. CONCLUSIONS: Heat shock protein 70 promotes lipogenesis in HepG2 cells. |
| DOI: | 10.1186/s12944-018-0722-8 |
| 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 |
| S04 | Anti-oxidative stress | oxidative stress | α-tocopherol: antioxidant | Vitamin E | 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 |
| T20 | Fatty acid synthase | FASN | inhibitor | Enzyme | P49327 | FAS_HUMAN | Details |
| T22 | Stearoyl-CoA desaturase | SCD | inhibitor | Enzyme | O00767 | SCD_HUMAN | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I14 | 9970 | Obesity | An overnutrition that is characterized by excess body fat, traditionally defined as an elevated ratio of weight to height (specifically 30 kilograms per meter squared), has_material_basis_in a multifactorial etiology related to excess nutrition intake, decreased caloric utilization, and genetic susceptibility, and possibly medications and certain disorders of metabolism, endocrine function, and mental illness. https://en.wikipedia.org/wiki/Obesity | disease of metabolism/acquired metabolic disease/ nutrition disease/overnutrition | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress |
|---|