Research Article Details
| Article ID: | A21695 |
| PMID: | 25112833 |
| Source: | J Endocrinol |
| Title: | Perinatal exposure to bisphenol A exacerbates nonalcoholic steatohepatitis-like phenotype in male rat offspring fed on a high-fat diet. |
| Abstract: | Bisphenol A (BPA) is one of the environmental endocrine disrupting chemicals, which is present ubiquitously in daily life. Accumulating evidence indicates that exposure to BPA contributes to metabolic syndrome. In this study, we examined whether perinatal exposure to BPA predisposed offspring to fatty liver disease: the hepatic manifestation of metabolic syndrome. Wistar rats were exposed to 50 μg/kg per day BPA or corn oil throughout gestation and lactation by oral gavage. Offspring were fed a standard chow diet (SD) or a high-fat diet (HFD) after weaning. Effects of BPA were assessed by examination of hepatic morphology, biochemical analysis, and the hepatic expression of genes and/or proteins involved in lipogenesis, fatty acid oxidation, gluconeogenesis, insulin signaling, inflammation, and fibrosis. On a SD, the offspring of rats exposed to BPA exhibited moderate hepatic steatosis and altered expression of insulin signaling elements in the liver, but with normal liver function. On a HFD, the offspring of rats exposed to BPA showed a nonalcoholic steatohepatitis-like phenotype, characterized by extensive accumulation of lipids, large lipid droplets, profound ballooning degeneration, impaired liver function, increased inflammation, and even mild fibrosis in the liver. Perinatal exposure to BPA worsened the hepatic damage caused by the HFD in the rat offspring. The additive effects of BPA correlated with higher levels of hepatic oxidative stress. Collectively, exposure to BPA may be a new risk factor for the development of fatty liver disease and further studies should assess whether this finding is also relevant to the human population. |
| DOI: | 10.1530/JOE-14-0356 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | Details |
| 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 | |
|---|---|---|---|---|---|
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D080 | Citrulline | Chemical drug | DB00155 | -- | -- | Under clinical trials | Details |
| D579 | Emfilermin | Miscellany | -- | adipocytes | Enhance lipid metabolism | Under investigation | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |