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Sex-Related Differences of Lipid Metabolism Induced by Triptolide: The Possible Role of the LXRα/SREBP-1 Signaling Pathway

Overview of attention for article published in Frontiers in Pharmacology, March 2016
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Title
Sex-Related Differences of Lipid Metabolism Induced by Triptolide: The Possible Role of the LXRα/SREBP-1 Signaling Pathway
Published in
Frontiers in Pharmacology, March 2016
DOI 10.3389/fphar.2016.00087
Pubmed ID
Authors

Zhenzhou Jiang, Xiao Huang, Shan Huang, Hongli Guo, Lu Wang, Xiaojiaoyang Li, Xin Huang, Tao Wang, Luyong Zhang, Lixin Sun

Abstract

Triptolide, a diterpenoid isolated from the plant Tripterygium wilfordii Hook. f., exerts a unique bioactive spectrum of anti-inflammatory and anticancer activities. However, triptolide's clinical applications are limited due to its severe toxicities. Fatty liver toxicity occurs in response to triptolide, and this toxic response significantly differs between males and females. This report investigated the pathogenesis underlying the sex-related differences in the dyslipidosis induced by triptolide in rats. Wistar rats were administered 0, 150, 300, or 450 μg triptolide/kg/day by gavage for 28 days. Ultrastructural examination revealed that more lipid droplets were present in female triptolide-treated rats than in male triptolide-treated rats. Furthermore, liver triglyceride, total bile acid and free fatty acid levels were significantly increased in female rats in the 300 and 450 μg/kg dose groups. The expression of liver X receptor α (LXRα) and its target genes, cholesterol 7α-hydroxylase (CYP7A1) and Sterol regulatory element-binding transcription factor 1(SREBP-1), increased following triptolide treatment in both male and female rats; however, the female rats were more sensitive to triptolide than the male rats. In addition, the expression of acetyl-CoA carboxylase 1(ACC1), a target gene of SREBP-1, increased in the female rats treated with 450 μg triptolide/kg/day, and ACC1 expression contributed to the sex-related differences in the triptolide-induced dysfunction of lipid metabolism. Our results demonstrate that the sex-related differences in LXR/SREBP-1-mediated regulation of gene expression in rats are responsible for the sex-related differences in lipid metabolism induced by triptolide, which likely underlie the sex-related differences in triptolide hepatotoxicity. This study will be important for predicting sex-related effects on the pharmacokinetics and toxicity of triptolide and for improving its safety.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 27 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 4%
Unknown 26 96%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 5 19%
Student > Master 3 11%
Professor 3 11%
Student > Bachelor 2 7%
Other 2 7%
Other 4 15%
Unknown 8 30%
Readers by discipline Count As %
Medicine and Dentistry 4 15%
Biochemistry, Genetics and Molecular Biology 4 15%
Pharmacology, Toxicology and Pharmaceutical Science 3 11%
Agricultural and Biological Sciences 1 4%
Unspecified 1 4%
Other 4 15%
Unknown 10 37%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 31 March 2016.
All research outputs
#20,317,110
of 22,858,915 outputs
Outputs from Frontiers in Pharmacology
#10,100
of 16,130 outputs
Outputs of similar age
#255,093
of 301,001 outputs
Outputs of similar age from Frontiers in Pharmacology
#65
of 94 outputs
Altmetric has tracked 22,858,915 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 16,130 research outputs from this source. They receive a mean Attention Score of 4.9. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 301,001 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 94 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.