Research Article Details
| Article ID: | A25355 |
| PMID: | 21932408 |
| Source: | Hepatology |
| Title: | Low doses of bisphenol A induce gene expression related to lipid synthesis and trigger triglyceride accumulation in adult mouse liver. |
| Abstract: | UNLABELLED: Changes in lifestyle are suspected to have strongly influenced the current obesity epidemic. Based on recent experimental, clinical, and epidemiological work, it has been proposed that some food contaminants may exert damaging effects on endocrine and metabolic functions, thereby promoting obesity and associated metabolic diseases such as nonalcoholic fatty liver disease (NAFLD). In this work, we investigated the effect of one suspicious food contaminant, bisphenol A (BPA), in vivo. We used a transcriptomic approach in male CD1 mice exposed for 28 days to different doses of BPA (0, 5, 50, 500, and 5,000 μg/kg/day) through food contamination. Data analysis revealed a specific impact of low doses of BPA on the hepatic transcriptome, more particularly on genes involved in lipid synthesis. Strikingly, the effect of BPA on the expression of de novo lipogenesis followed a nonmonotonic dose-response curve, with more important effects at lower doses than at the higher dose. In addition to lipogenic enzymes (Acc, Fasn, Scd1), the expression of transcription factors such as liver X Receptor, the sterol regulatory element binding protein-1c, and the carbohydrate responsive element binding protein that govern the expression of lipogenic genes also followed a nonmonotonic dose-response curve in response to BPA. Consistent with an increased fatty acid biosynthesis, determination of fat in the liver showed an accumulation of cholesteryl esters and of triglycerides. CONCLUSION: Our work suggests that exposure to low BPA doses may influence de novo fatty acid synthesis through increased expression of lipogenic genes, thereby contributing to hepatic steatosis. Exposure to such contaminants should be carefully examined in the etiology of metabolic diseases such as NAFLD and nonalcoholic steatohepatitis. |
| DOI: | 10.1002/hep.24685 |
| 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 | |
|---|---|---|---|---|---|---|---|
| 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 |