Skip Navigation
Skip to contents

Endocrinol Metab : Endocrinology and Metabolism

clarivate
OPEN ACCESS
SEARCH
Search

Author index

Page Path
HOME > BROWSE ARTICLES > Author index
Search
Dae Hyun Kim 2 Articles
Diabetes, obesity and metabolism
FoxO6-Mediated TXNIP Induces Lipid Accumulation in the Liver through NLRP3 Inflammasome Activation
Mi Eun Kim, Jun Sik Lee, Tae Won Kim, Min Hi Park, Dae Hyun Kim
Endocrinol Metab. 2024;39(1):127-139.   Published online February 22, 2024
DOI: https://doi.org/10.3803/EnM.2023.1826
  • 2,206 View
  • 65 Download
  • 1 Web of Science
  • 1 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Hepatic steatosis, which involves the excessive accumulation of lipid droplets in hepatocytes, presents a significant global health concern due to its association with obesity and metabolic disorders. Inflammation plays a crucial role in the progression of hepatic steatosis; however, the precise molecular mechanisms responsible for this process remain unknown.
Methods
This study investigated the involvement of the nucleotide-binding oligomerization domain-like receptor pyrin domain-containing-3 (NLRP3) inflammasome and the forkhead box O6 (FoxO6) transcription factor in the pathogenesis of hepatic steatosis. We monitored the NLRP3 inflammasome and lipogenesis in mice overexpressing the constitutively active (CA)-FoxO6 allele and FoxO6-null mice. In an in vitro study, we administered palmitate to liver cells overexpressing CA-FoxO6 and measured changes in lipid metabolism.
Results
We administered palmitate treatment to clarify the mechanisms through which FoxO6 activates cytokine interleukin (IL)-1β through the NLRP3 inflammasome. The initial experiments revealed that dephosphorylation led to palmitate-induced FoxO6 transcriptional activity. Further palmitate experiments showed increased expression of IL-1β and the hepatic NLRP3 inflammasome complex, including adaptor protein apoptotic speck protein containing a caspase recruitment domain (ASC) and pro-caspase-1. Furthermore, thioredoxin-interacting protein (TXNIP), a key regulator of cellular redox conditions upstream of the NLRP3 inflammasome, was induced by FoxO6 in the liver and HepG2 cells.
Conclusion
The findings of this study shed light on the molecular mechanisms underpinning the FoxO6-NLRP3 inflammasome axis in promoting inflammation and lipid accumulation in the liver.

Citations

Citations to this article as recorded by  
  • Identifying differentially expressed genes in goat mammary epithelial cells induced by overexpression of SOCS3 gene using RNA sequencing
    Ning Song, Cunxia Ma, Yuzhu Guo, Shuangshuang Cui, Shihao Chen, Zhi Chen, Yinghui Ling, Yunhai Zhang, Hongyu Liu
    Frontiers in Veterinary Science.2024;[Epub]     CrossRef
Close layer
Endocrine Research
Mechanism of Lipid Accumulation through PAR2 Signaling in Diabetic Male Mice
Dae Hyun Kim, Ye Ra Kim, EunJin Bang, Sugyeong Ha, Sang Gyun Noh, Byeong Moo Kim, Seong Ho Jeong, Hee Jin Jung, Ji Young Lee, Hae Young Chung
Endocrinol Metab. 2021;36(1):171-184.   Published online February 24, 2021
DOI: https://doi.org/10.3803/EnM.2020.850
  • 5,169 View
  • 143 Download
  • 5 Web of Science
  • 5 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Protease-activated protein-2 (PAR2) has been reported to regulate hepatic insulin resistance condition in type 2 diabetes mice. However, the mechanism of lipid metabolism through PAR2 in obesity mice have not yet been examined. In liver, Forkhead box O1 (FoxO1) activity induces peroxisome proliferator-activated receptor γ (PPARγ), leading to accumulation of lipids and hyperlipidemia. Hyperlipidemia significantly influence hepatic steatoses, but the mechanisms underlying PAR2 signaling are complex and have not yet been elucidated.
Methods
To examine the modulatory action of FoxO1 and its altered interaction with PPARγ, we utilized db/db mice and PAR2-knockout (KO) mice administered with high-fat diet (HFD).
Results
Here, we demonstrated that PAR2 was overexpressed and regulated downstream gene expressions in db/db but not in db+ mice. The interaction between PAR2/β-arrestin and Akt was also greater in db/db mice. The Akt inhibition increased FoxO1 activity and subsequently PPARγ gene in the livers that led to hepatic lipid accumulation. Our data showed that FoxO1 was negatively controlled by Akt signaling and consequently, the activity of a major lipogenesis-associated transcription factors such as PPARγ increased, leading to hepatic lipid accumulation through the PAR2 pathway under hyperglycemic conditions in mice. Furthermore, the association between PPARγ and FoxO1 was increased in hepatic steatosis condition in db/db mice. However, HFD-fed PAR2-KO mice showed suppressed FoxO1-induced hepatic lipid accumulation compared with HFD-fed control groups.
Conclusion
Collectively, our results provide evidence that the interaction of FoxO1 with PPARγ promotes hepatic steatosis in mice. This might be due to defects in PAR2/β-arrestin-mediated Akt signaling in diabetic and HFD-fed mice.

Citations

Citations to this article as recorded by  
  • β-Sitosterol Reduces the Content of Triglyceride and Cholesterol in a High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease Zebrafish (Danio rerio) Model
    Peng Zhang, Naicheng Liu, Mingyang Xue, Mengjie Zhang, Zidong Xiao, Chen Xu, Yuding Fan, Junqiang Qiu, Qinghua Zhang, Yong Zhou
    Animals.2024; 14(9): 1289.     CrossRef
  • Par2-mediated responses in inflammation and regeneration: choosing between repair and damage
    Gal Reches, Ron Piran
    Inflammation and Regeneration.2024;[Epub]     CrossRef
  • Betaine Suppresses Lipid Accumulation in Liver: Inhibition of FoxO6 and PPARγ Interaction
    Min Hi Park, Dae Hyun Kim
    Journal of Medicinal Food.2024;[Epub]     CrossRef
  • Biochanin‐A has antidiabetic, antihyperlipidemic, antioxidant, and protective effects on diabetic nephropathy via suppression of TGF‐β1 and PAR‐2 genes expression in kidney tissues of STZ‐induced diabetic rats
    Jamal Amri, Mona Alaee, Rasool Babaei, Zahra Salemi, Reza Meshkani, Ali Ghazavi, Ahmad Akbari, Mehdi Salehi
    Biotechnology and Applied Biochemistry.2022; 69(5): 2112.     CrossRef
  • Delineation of the healthy rabbit liver by immunohistochemistry – A technical note
    Gabriella Meier Bürgisser, Olivera Evrova, Dorothea M. Heuberger, Julia Rieber, Pietro Giovanoli, Maurizio Calcagni, Johanna Buschmann
    Acta Histochemica.2021; 123(7): 151795.     CrossRef
Close layer

Endocrinol Metab : Endocrinology and Metabolism
TOP