TXN, a Xanthohumol Derivative, Significantly Attenuates High-Fat Diet Induced Hepatic Steatosis In Vivo by Antagonizing PPARγ
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA691470 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13415009.fastq.gz | Fastqsanger.gz | |||
| SRR13415010.fastq.gz | Fastqsanger.gz | |||
| SRR13415011.fastq.gz | Fastqsanger.gz | |||
| SRR13415012.fastq.gz | Fastqsanger.gz | |||
| SRR13415013.fastq.gz | Fastqsanger.gz |
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Project description:We previously reported xanthohumol (XN), and its synthetic derivative tetrahydro-XN (TXN), attenuates high-fat diet (HFD)-induced obesity and metabolic syndrome in C57Bl/6J mice. The objective of the current study was to determine the effect of XN and TXN on lipid accumulation in the liver. Non-supplemented mice were unable to adapt their caloric intake to 60% HFD, resulting in obesity and hepatic steatosis; however, TXN reduced weight gain and decreased hepatic steatosis. Liver transcriptomics indicated that TXN might antagonize lipogenic PPARγ actions in vivo. XN and TXN inhibited rosiglitazone-induced 3T3-L1 cell differentiation concomitant with decreased expression of lipogenesis-related genes. A peroxisome proliferator activated receptor gamma (PPARγ) competitive binding assay showed that XN and TXN bind to PPARγ with an IC50 similar to pioglitazone and 8-10 times stronger than oleate. Molecular docking simulations demonstrated that XN and TXN bind in the PPARγ ligand-binding domain pocket. Our findings are consistent with XN and TXN acting as antagonists of PPARγ.
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