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LDL Cholesterol Uptake Assay Using Live Cell Imaging Analysis with Cell Health Monitoring
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SIRT1 regulates hepatic vldlr levels.

Mona Peyman1,2,3,4, Anna Babin-Ebell1,2,3,4, Rosalía Rodríguez-Rodríguez5,6

  • 1Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, Barcelona, Spain.

Cell Communication and Signaling : CCS
|May 28, 2024
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Sirtuin 1 (SIRT1) activation reduces fatty liver by lowering very low-density lipoprotein receptor (VLDLR) levels. This study reveals SIRT1

Keywords:
ER stressHIF-1αMASLDSIRT1VLDLR

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Area of Science:

  • Metabolic disease research
  • Liver disease mechanisms
  • Cellular signaling pathways

Background:

  • Endoplasmic reticulum (ER) stress increases hepatic very low-density lipoprotein receptor (VLDLR) levels, promoting fatty liver.
  • VLDLR facilitates the uptake of triglyceride-rich lipoproteins into the liver.

Purpose of the Study:

  • To investigate if sirtuin 1 (SIRT1) regulates hepatic lipid accumulation.
  • To determine if SIRT1 modulates VLDLR levels and subsequent lipoprotein uptake.

Main Methods:

  • Utilized rat models fed fructose, Sirt1 knockout mice, and tunicamycin-treated mice.
  • Employed human hepatoma cells with siRNA, tunicamycin, or specific inhibitors.
  • Assessed hepatic VLDLR and SIRT1 protein levels, and gene expression.

Main Results:

  • Fructose-fed rats and Sirt1 knockout mice showed reduced SIRT1 and increased VLDLR levels.
  • SIRT1 inhibition in human cells upregulated VLDLR, dependent on hypoxia-inducible factor 1α (HIF-1α).
  • SIRT1 activation in mice prevented tunicamycin-induced VLDLR increase.

Conclusions:

  • SIRT1 plays a protective role in fatty liver development.
  • SIRT1 attenuates fatty liver by negatively regulating hepatic VLDLR levels.