Research Article Details
| Article ID: | A10711 |
| PMID: | 31226595 |
| Source: | J Hazard Mater |
| Title: | Chronic exposure to tetrabromodiphenyl ether (BDE-47) aggravates hepatic steatosis and liver fibrosis in diet-induced obese mice. |
| Abstract: | Exposure to polybrominated diphenyl ethers (PBDEs), is closely associated with the occurrence of obesity and non-alcoholic fatty liver disease (NAFLD), yet their pathological effects and underlying mechanisms remain unclear. To examine the role of 2, 2', 4, 4'-tetrabromodiphenyl ether (BDE-47) in the progression of NAFLD under obese condition, male C57BL/6 J mice were fed with diet interaction for 15 weeks and subcutaneously injected with BDE-47 (7 mg/kg or 70 mg/kg) or the vehicle weekly. BDE-47 exposure (70 mg/kg) significantly elevated the body weight and worsened hepatic steatosis along with increased inflammation in high fat diet (HFD) fed mice. Furthermore, integration analysis of lipidomics and gene expression revealed that BDE-47 up-regulated triglyceride synthesis but suppressed lipid exportation and β oxidation, aggravating the accumulation of hepatic lipid in HFD fed mice. In addition, the increase of liver fibrosis, serum transaminase levels, as well as lipid peroxidation have been observed in mice co-treated with BDE-47 and HFD. Moreover, BDE-47-induced fibrogenic responses in hepatocytes were suppressed by antioxidants, which confirmed that BDE-47-induced liver fibrosis was tightly associated with oxidative stress. In conclusion, these results provided new and robust evidence for revealing the hepatoxicity of BDE-47 under obese condition and illustrated the underlying mechanism of BDE-47 induced liver fibrosis. |
| DOI: | 10.1016/j.jhazmat.2019.120766 |
| 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 |
| S03 | Anti-fibrosis | fibrosis | Angiotensin Receptor Blocker (ARB); CCR2/CCR5 antagonist; Thyroid receptor β agonist; PEGylated human FGF21 analogue; Monoclonal antibody to lysyl oxidase-like 2 (LOXL2); Galectin-3 inhibitor; FGF19 variant | Losartan; Cenicriviroc; VK-2809; MGL-3196; Pegbelfermin; Simtuzumab; GR-MD-02; NGM282 | Details |
| S04 | Anti-oxidative stress | oxidative stress | α-tocopherol: antioxidant | Vitamin E | 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 | |
|---|---|---|---|---|---|---|---|
| D080 | Citrulline | Chemical drug | DB00155 | -- | -- | Under clinical trials | Details |
| 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 |