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Obesity

Obesity

IF: 4.2
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Rutaecarpin reduces lipids by DGKθ-dependent activation of PPARα.

Published:23 November 2022 DOI: 10.1002/oby.23572 PMID: 36415997
Di Wu, Jiheng Wang, Yongxing Chang, Shiyu Zhang, Jinfeng Liang, Junli Zhao, Peiyan Yang, Qinwen Mao, Haibin Xia

Abstract

Objective

Lipid metabolic disorders pose a serious threat to human health, and currently no good treatments exist. In earlier studies by the authors, HepG2 cells with diacylglycerol kinase theta (DGKθ) knockout were found to cause significant lipid accumulation, suggesting that DGKθ may be a potential target for treating lipid metabolic disorders.

Methods

A high-throughput screening?of natural products targeting the potential signaling pathway of lipid metabolism was carried out in the DGKθ-T2A-luciferase knock-in HepG2 cell. RNA-sequencing?and bioinformatic approaches were used to analyze the potential pathway by which rutaecarpin decreases lipids. Western blot and quantitative polymerase chain reaction?were performed to investigate the mechanisms of rutaecarpin's reduction in lipid levels.

Results

Rutaecarpin was found to significantly enhance DGKθ expression, and the potential mechanisms by which rutaecarpin accelerates lipid metabolism by targeting DGKθ was explored in vitro and in vivo. The results indicated that rutaecarpin could markedly reduce lipid accumulation in oleic acid-induced HepG2 cells and in high-fat diet-induced obese C57BL/6J mice by targeting the hepatocyte nuclear factor 1-beta (HNF1B)-DGKθ-peroxisome proliferator-activated receptor alpha (PPARα)-apolipoprotein C3 (APOC3) pathway.

Conclusion

Rutaecarpin is effective in reducing lipid accumulation, and the development of a high-throughput screening platform based on a reporter knock-in cell line may facilitate the discovery of effective drugs for lipid metabolic disorders based on the DGKθ target.

Substances (4)

Materials
Procduct Name CAS Molecular Formula Supplier Price
DIACYLGLYCEROL KINASE INHIBITOR II 120166-69-0 C28H25F2N3OS 66 suppliers $32.00-$2500.00
DIACYLGLYCEROL KINASE INHIBITOR II 120166-69-0 C28H25F2N3OS 66 suppliers $32.00-$2500.00
DIACYLGLYCEROL KINASE INHIBITOR II 120166-69-0 C28H25F2N3OS 66 suppliers $32.00-$2500.00
DIACYLGLYCEROL KINASE INHIBITOR II 120166-69-0 C28H25F2N3OS 66 suppliers $32.00-$2500.00

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