PUBLICATION

Bisphenol A induces fatty liver by an endocannabinoid-mediated positive feedback loop

Authors
Martella, A., Silvestri, C., Maradonna, F., Gioacchini, G., AllarĂ , M., Radaelli, G., Overby, D.R., Di Marzo, V., Carnevali, O.
ID
ZDB-PUB-160326-3
Date
2016
Source
Endocrinology   157(5): 1751-63 (Journal)
Registered Authors
Carnevali, Oliana
Keywords
none
MeSH Terms
  • Animals
  • Arachidonic Acids/metabolism*
  • Benzhydryl Compounds*
  • Cell Line
  • Endocannabinoids/metabolism*
  • Endocrine Disruptors*
  • Ethanolamines/metabolism
  • Fatty Liver/chemically induced*
  • Fatty Liver/metabolism*
  • Feedback, Physiological/drug effects*
  • Glycerides/metabolism*
  • Hepatocytes/drug effects
  • Hepatocytes/metabolism
  • Humans
  • Liver/drug effects*
  • Liver/metabolism
  • Palmitic Acids/metabolism
  • Phenols*
  • Polyunsaturated Alkamides/metabolism*
  • Receptor, Cannabinoid, CB1/metabolism
  • Triglycerides/metabolism
  • Zebrafish
  • Zebrafish Proteins/metabolism
PubMed
27014939 Full text @ Endocrinology
CTD
27014939
Abstract
The xenoestrogen bisphenol A (BPA) is a widespread plasticizer detectable within several ecosystems. BPA is considered a metabolic disruptor affecting different organs; however, little is known about its mechanism of action in the liver, where it triggers triglyceride accumulation. Exposed adult zebrafish (Danio rerio) to BPA developed hepatosteatosis, which was associated with an increase in the liver levels of the obesogenic endocannabinoids 2-AG and anandamide and a concomitant decrease in palmitoylethanolamide. These changes were associated with variations in the expression of key endocannabinoid catabolic and metabolic enzymes and an increase in the expression of the endocannabinoid receptor cnr1. Acute and chronic in vitro treatments with nano and micromolar BPA doses, showed increased anandamide levels in line with decreased activity of FAAH, the main anandamide hydrolytic enzyme, and induced triglyceride accumulation in HHL-5 cells in a CB1-dependent manner. We conclude that BPA is able to produce hepatosteatosis in zebrafish and human hepatocytes by upregulating the endocannabinoid system.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping