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Miyazaki T, Honda A, Ikegami T, et al. Human-specific dual regulations of FXR-activation for reduction of fatty liver using . J Clin Biochem Nutr. 2018;64(2):112-123doi: 10.3164/jcbn.18-80.
Miyazaki, T., Honda, A., Ikegami, T., Iida, T., & Matsuzaki, Y. (2019). Human-specific dual regulations of FXR-activation for reduction of fatty liver using . Journal of clinical biochemistry and nutrition, 64(2), 112-123. https://doi.org/10.3164/jcbn.18-80
Miyazaki, Teruo, et al. "Human-specific dual regulations of FXR-activation for reduction of fatty liver using ." Journal of clinical biochemistry and nutrition vol. 64,2 (2019): 112-123. doi: https://doi.org/10.3164/jcbn.18-80
Miyazaki T, Honda A, Ikegami T, Iida T, Matsuzaki Y. Human-specific dual regulations of FXR-activation for reduction of fatty liver using . J Clin Biochem Nutr. 2019 Mar;64(2):112-123. doi: 10.3164/jcbn.18-80. Epub 2018 Nov 28. PMID: 30936623; PMCID: PMC6436045.
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J Clin Biochem Nutr. 2019 Mar;64(2):112-123. doi: 10.3164/jcbn.18-80. Epub 2018 Nov 28.

Human-specific dual regulations of FXR-activation for reduction of fatty liver using .

Journal of clinical biochemistry and nutrition

Teruo Miyazaki, Akira Honda, Tadashi Ikegami, Takashi Iida, Yasushi Matsuzaki

Affiliations

  1. Joint Research Center, Tokyo Medical University Ibaraki Medical Center, 3-20-1 Chuo, Ami, Inashiki, Ibaraki 300-0395, Japan.
  2. Department of Internal Medicine, Division of Gastroenterology and Hepatology, Tokyo Medical University Ibaraki Medical Center, 3-20-1 Chuo, Ami, Inashiki, Ibaraki 300-0395, Japan.
  3. Department of Chemistry, College of Humanities and Sciences, Nihon University, 3-25-40 Sakurajosui, Setagaya-ku, Tokyo 156-8550, Japan.

PMID: 30936623 PMCID: PMC6436045 DOI: 10.3164/jcbn.18-80

Abstract

Nuclear receptor farnesoid X receptor activation inhibits fatty acid synthesis through the liver X receptor-α-sterol regulatory element binding protein-1c pathway universally in animals, but also has human-specific crosstalk with the peroxisome proliferator-activated receptor-α. The effects of farnesoid X receptor-ligands on both the synthesis and degradation of fatty liver through nuclear receptor-related regulation were investigated in both human and murine hepatocytes. A fatty liver culture cell model was established using a synthetic liver X receptor-α-ligand (To901317) for both human and mouse non-neoplastic hepatocytes. The hepatocytes were exposed to natural or synthetic farnesoid X receptor-ligands (bile acids, GW4064, obeticholic acid) together with or after To901317. Cellular triglyceride accumulation was significantly inhibited by the farnesoid X receptor-ligands along with inhibition of lipogenic genes and up-regulation of farnesoid X receptor-target small heterodimer partner in both human and mouse cells. The accumulated triglyceride was significantly degraded by the farnesoid X receptor-ligands only in the human cells accompanied with the up-regulations of peroxisome proliferator-activated receptor-α and fatty acid β-oxidation. Farnesoid X receptor-ligands can be therapeutic agents for treating human fatty liver through dual effects on inhibition of lipogenesis and on enhancement of lipolysis.

Keywords: bile acids; fatty liver; human-specific crosstalk; lipolysis; nuclear receptor ligand

Conflict of interest statement

No potential conflicts of interest were disclosed.

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