Dataset Information

Bisphenol A sulfonation is impaired in metabolic and liver disease.

ABSTRACT:

Background

Bisphenol A (BPA) is a widely used industrial chemical and suspected endocrine disruptor to which humans are ubiquitously exposed. The liver metabolizes and facilitates BPA excretion through glucuronidation and sulfonation. The sulfotransferase enzymes contributing to BPA sulfonation (detected in human and rodents) is poorly understood.

Objectives

To determine the impact of metabolic and liver disease on BPA sulfonation in human and mouse livers.

Methods

The capacity for BPA sulfonation was determined in human liver samples that were categorized into different stages of metabolic and liver disease (including obesity, diabetes, steatosis, and cirrhosis) and in livers from ob/ob mice.

Results

In human liver tissues, BPA sulfonation was substantially lower in livers from subjects with steatosis (23%), diabetes cirrhosis (16%), and cirrhosis (18%), relative to healthy individuals with non-fatty livers (100%). In livers of obese mice (ob/ob), BPA sulfonation was lower (23%) than in livers from lean wild-type controls (100%). In addition to BPA sulfonation activity, Sult1a1 protein expression decreased by 97% in obese mouse livers.

Conclusion

Taken together these findings establish a profoundly reduced capacity of BPA elimination via sulfonation in obese or diabetic individuals and in those with fatty or cirrhotic livers versus individuals with healthy livers.

SUBMITTER: Yalcin EB

PROVIDER: S-EPMC4724572 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Publications

Bisphenol A sulfonation is impaired in metabolic and liver disease.

Yalcin Emine B EB Kulkarni Supriya R SR Slitt Angela L AL King Roberta R

Toxicology and applied pharmacology 20151219

<h4>Background</h4>Bisphenol A (BPA) is a widely used industrial chemical and suspected endocrine disruptor to which humans are ubiquitously exposed. The liver metabolizes and facilitates BPA excretion through glucuronidation and sulfonation. The sulfotransferase enzymes contributing to BPA sulfonation (detected in human and rodents) is poorly understood.<h4>Objectives</h4>To determine the impact of metabolic and liver disease on BPA sulfonation in human and mouse livers.<h4>Methods</h4>The capa ...[more]

PMID: 26712468

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Project description:RelA, also known as nuclear factor kappa B p65, plays a crucial role in the pathogenesis of various liver diseases. However, the specific role of RelA in hepatocytes during the progression of metabolic dysfunction-associated steatotic liver disease (MASLD) is not well understood. This study explored the relationship between impaired RelA signaling and lipid metabolism disorders in hepatocytes, and how they synergistically contribute to the advancement of MASLD. We assessed the changes, regulatory relationships, and impacts of RelA signaling and lipid metabolism remodeling on disease progression both in vitro and in vivo. During MASLD, there was a decrease in the expression of RelA and hepatocyte nuclear factor 1 alpha (HNF1α), with both factors showing mutual enhancement of each other's expression under normal conditions. This synergistic effect was absent during hepatocyte steatosis. RelA or HNF1α depletion in hepatocytes intensified MASLD symptoms, whereas overexpression of RELA or treatment with necrostatin-1 (a necroptosis inhibitor) or Z-VAD (a caspase inhibitor) significantly mitigated these effects. Mechanistically, during hepatic steatosis, altered lipid profiles exhibited lipotoxicity, inducing hepatocyte apoptosis and necroptosis, whereas endoplasmic reticulum (ER) stress triggered lipid remodeling processes similar to those observed in MASLD. RelA signaling upregulated the expression of activating transcription factor 4 and glucose-regulated protein 78, thereby alleviating ER stress. Impaired RelA signaling remodeled the ER stress response and lipid metabolism, and enhanced lipid accumulation and lipid toxicity. In conclusion, impaired RelA signaling and disrupted lipid metabolism form a detrimental feedback loop in hepatocytes that promotes MASLD progression. Lipid accumulation suppresses RelA signaling, remodeling the ER stress response and exacerbating lipid metabolism disorder, ultimately leading to hepatocyte apoptosis and necroptosis.

Dataset Information

Bisphenol A sulfonation is impaired in metabolic and liver disease.

Background

Objectives

Methods

Results

Conclusion

Publications

Bisphenol A sulfonation is impaired in metabolic and liver disease.

Similar Datasets

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