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Review Article
Obesity and Metabolism
Bile Acid Nuclear Receptor Farnesoid X Receptor: Therapeutic Target for Nonalcoholic Fatty Liver Disease
Sun-Gi Kim, Byung-Kwon Kim, Kyumin Kim, Sungsoon Fang
Endocrinol Metab. 2016;31(4):500-504.   Published online December 20, 2016
DOI: https://doi.org/10.3803/EnM.2016.31.4.500
  • 6,768 View
  • 76 Download
  • 35 Web of Science
  • 36 Crossref
AbstractAbstract PDFPubReader   

Nonalcoholic fatty liver disease (NAFLD) is one of the causes of fatty liver, occurring when fat is accumulated in the liver without alcohol consumption. NAFLD is the most common liver disorder in advanced countries. NAFLD is a spectrum of pathology involving hepatic steatosis with/without inflammation and nonalcoholic steatohepatitis with accumulation of hepatocyte damage and hepatic fibrosis. Recent studies have revealed that NAFLD results in the progression of cryptogenic cirrhosis that leads to hepatocarcinoma and cardiovascular diseases such as heart failure. The main causes of NAFLD have not been revealed yet, metabolic syndromes including obesity and insulin resistance are widely accepted for the critical risk factors for the pathogenesis of NAFLD. Nuclear receptors (NRs) are transcriptional factors that sense environmental or hormonal signals and regulate expression of genes, involved in cellular growth, development, and metabolism. Several NRs have been reported to regulate genes involved in energy and xenobiotic metabolism and inflammation. Among various NRs, farnesoid X receptor (FXR) is abundantly expressed in the liver and a key regulator to control various metabolic processes in the liver. Recent studies have shown that NAFLD is associated with inappropriate function of FXR. The impact of FXR transcriptional activity in NAFLD is likely to be potential therapeutic strategy, but still requires to elucidate underlying potent therapeutic mechanisms of FXR for the treatment of NAFLD. This article will focus the physiological roles of FXR and establish the correlation between FXR transcriptional activity and the pathogenesis of NAFLD.

Citations

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Original Articles
Endocrine Research
Thyroid Hormone Regulates the mRNA Expression of Small Heterodimer Partner through Liver Receptor Homolog-1
Hwa Young Ahn, Hwan Hee Kim, Ye An Kim, Min Kim, Jung Hun Ohn, Sung Soo Chung, Yoon-Kwang Lee, Do Joon Park, Kyong Soo Park, David D. Moore, Young Joo Park
Endocrinol Metab. 2015;30(4):584-592.   Published online December 31, 2015
DOI: https://doi.org/10.3803/EnM.2015.30.4.584
  • 4,616 View
  • 41 Download
  • 5 Web of Science
  • 5 Crossref
AbstractAbstract PDFPubReader   
Background

Expression of hepatic cholesterol 7α-hydroxylase (CYP7A1) is negatively regulated by orphan nuclear receptor small heterodimer partner (SHP). In this study, we aimed to find whether thyroid hormone regulates SHP expression by modulating the transcriptional activities of liver receptor homolog-1 (LRH-1).

Methods

We injected thyroid hormone (triiodothyronine, T3) to C57BL/6J wild type. RNA was isolated from mouse liver and used for microarray analysis and quantitative real-time polymerase chain reaction (PCR). Human hepatoma cell and primary hepatocytes from mouse liver were used to confirm the effect of T3 in vitro. Promoter assay and electrophoretic mobility-shift assay (EMSA) were also performed using human hepatoma cell line

Results

Initial microarray results indicated that SHP expression is markedly decreased in livers of T3 treated mice. We confirmed that T3 repressed SHP expression in the liver of mice as well as in mouse primary hepatocytes and human hepatoma cells by real-time PCR analysis. LRH-1 increased the promoter activity of SHP; however, this increased activity was markedly decreased after thyroid hormone receptor β/retinoid X receptor α/T3 administration. EMSA revealed that T3 inhibits specific LRH-1 DNA binding.

Conclusion

We found that thyroid hormone regulates the expression of SHP mRNA through interference with the transcription factor, LRH-1.

Citations

Citations to this article as recorded by  
  • Metabolic Dysfunction–Associated Steatotic Liver Disease: From Pathogenesis to Current Therapeutic Options
    Piero Portincasa, Mohamad Khalil, Laura Mahdi, Valeria Perniola, Valeria Idone, Annarita Graziani, Gyorgy Baffy, Agostino Di Ciaula
    International Journal of Molecular Sciences.2024; 25(11): 5640.     CrossRef
  • Safety and efficacy of resmetirom in metabolic dysfunction-associated steatohepatitis (MASH): a systemic review and meta-analysis
    Laraib Abbasi, Qunoot Irfan, Syed Muhammad Mehdi Zaidi, Izma Jawed, Abdullah Malik, Shamama Kaleem
    European Journal of Gastroenterology & Hepatology.2024;[Epub]     CrossRef
  • Bile acid and receptors: biology and drug discovery for nonalcoholic fatty liver disease
    Ting-ying Jiao, Yuan-di Ma, Xiao-zhen Guo, Yun-fei Ye, Cen Xie
    Acta Pharmacologica Sinica.2022; 43(5): 1103.     CrossRef
  • Loperamide induces excessive accumulation of bile acids in the liver of mice with different diets
    Zili Lei, Hedong Rong, Yanhong Yang, Siping Yu, Tianle Zhang, Lei Chen, Ya Nie, Qi Song, Qing Hu, Jiao Guo
    Toxicology.2022; 477: 153278.     CrossRef
  • Pathogenesis of hypothyroidism-induced NAFLD is driven by intra- and extrahepatic mechanisms
    Giuseppe Ferrandino, Rachel R. Kaspari, Olga Spadaro, Andrea Reyna-Neyra, Rachel J. Perry, Rebecca Cardone, Richard G. Kibbey, Gerald I. Shulman, Vishwa Deep Dixit, Nancy Carrasco
    Proceedings of the National Academy of Sciences.2017;[Epub]     CrossRef
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Effect of Thyroid Hormone to the Expression of Bile Salt Export Pump.
Hwa Young Ahn, Kwan Jae Lee, Soon Hui Kim, Eun Ky Kim, Ah Reum Kang, Jung Ah Lim, Ji Won Yoon, Kyung Won Kim, Do Joon Park, Bo Youn Cho, Young Joo Park
Endocrinol Metab. 2011;26(3):232-238.   Published online September 1, 2011
DOI: https://doi.org/10.3803/EnM.2011.26.3.232
  • 66,724 View
  • 30 Download
  • 3 Crossref
AbstractAbstract PDF
BACKGROUND
Bile acids were important for the regulation of cholesterol homeostasis. Thyroid hormone increased the expression of CYP7A1 (cholesterol 7alpha-hydroxylase), catalyzing the first step in the biosynthesis of bile acids. However, the effect of thyroid hormone on bile acid export has not been previously assessed. The principal objective of this study is to evaluate the effects of thyroid hormone on the bile salt export pump (BSEP). METHODS: Thyroid hormone, T3 (1 mg/g) was administered to male mice via intraperitoneal injection. After 6 hours and 5 days of T3 treatment, we measured serum total and LDL cholesterol and hepatobiliary bile acid concentrations. We assessed the changes associated with bile acid synthesis and transport. In order to evaluate the direct effect of thyroid hormone, we assessed the changes in the levels of BSEP protein after T3 administration in human hepatoma cells. RESULTS: Serum total and LDL cholesterol were reduced and hepatobiliary bile acid concentrations were increased following T3 treatment. Expressions of Cyp7a1 and BSEP mRNA were increased following T3 treatment. The levels of the BSEP protein in the mouse liver as well as in the human hepatoma cells were increased after T3 treatment. CONCLUSION: Thyroid hormone can regulate LDL cholesterol metabolism. It increases bile acid synthesis and the excretion of bile acids via increased BSEP expression.

Citations

Citations to this article as recorded by  
  • Hypothyroidism Increases Cholesterol Gallstone Prevalence in Mice by Elevated Hydrophobicity of Primary Bile Acids
    Irina Kube, Luca Bartolomeo Tardio, Ute Hofmann, Ahmed Ghallab, Jan G. Hengstler, Dagmar Führer, Denise Zwanziger
    Thyroid.2021; 31(6): 973.     CrossRef
  • Thyroid Dysfunction and Cholesterol Gallstone Disease
    Irina Kube, Denise Zwanziger
    Experimental and Clinical Endocrinology & Diabetes.2020; 128(06/07): 455.     CrossRef
  • Thyroid hormone receptor β1 stimulates ABCB4 to increase biliary phosphatidylcholine excretion in mice
    Julien Gautherot, Thierry Claudel, Frans Cuperus, Claudia Daniela Fuchs, Thomas Falguières, Michael Trauner
    Journal of Lipid Research.2018; 59(9): 1610.     CrossRef
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