Resveratrol administration or SIRT1 overexpression does not increase LXR signaling and macrophage-to-feces reverse cholesterol transport in vivo

Transl Res. 2013 Feb;161(2):110-7. doi: 10.1016/j.trsl.2012.10.008. Epub 2012 Nov 10.

Abstract

The natural polyphenol resveratrol has cardiometabolic protective properties. Resveratrol has been reported to be an activator of NAD+-dependent deacetylase sirtuin 1 (SIRT1), which may regulate liver X receptor (LXR) activity, thereby upregulating the expression of genes crucial in reverse cholesterol transport (RCT). In the present study, the effects of resveratrol and SIRT1 overexpression on RCT from macrophages-to-feces in vivo in C57BL/6 mice were determined. [³H]cholesterol-labeled mouse macrophages were injected intraperitoneally into mice treated with intragastric doses of the well-known LXR agonist T0901317, resveratrol, or a vehicle solution, and radioactivity was determined in plasma, liver, and feces. T0901317-treated mice presented increased [³H]cholesterol in plasma and HDL 48 h after the label injection. Treatment with T0901317 also increased liver ABCA1, G1, and G5 gene expression and reduced intestinal cholesterol absorption which were changes that were associated with a 2.8-fold increase in macrophage-derived [³H]cholesterol in feces. In contrast, resveratrol treatment had no effect on liver LXR signaling or fecal [³H]cholesterol excretion. A separate experiment was conducted in SIRT1 transgenic mice. Liver LXR-target gene expression and magnitude of macrophage-derived [³H]cholesterol in plasma, liver, and feces of SIRT1 transgenic mice did not differ from those of wild-type mice. We conclude that neither resveratrol administration nor SIRT1 overexpression upregulate liver LXR-target genes and macrophage-to-feces RCT in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Biological Transport / drug effects
  • Cell Line
  • Cholesterol / metabolism*
  • Feces / chemistry
  • Female
  • Gene Expression / drug effects
  • Hydrocarbons, Fluorinated / pharmacology
  • Liver / drug effects
  • Liver / metabolism
  • Liver X Receptors
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Orphan Nuclear Receptors / metabolism*
  • Resveratrol
  • Signal Transduction
  • Sirtuin 1 / genetics*
  • Sirtuin 1 / metabolism
  • Stilbenes / pharmacology*
  • Sulfonamides / pharmacology

Substances

  • Antioxidants
  • Hydrocarbons, Fluorinated
  • Liver X Receptors
  • Orphan Nuclear Receptors
  • Stilbenes
  • Sulfonamides
  • TO-901317
  • Cholesterol
  • Sirt1 protein, mouse
  • Sirtuin 1
  • Resveratrol