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

Joan Carles Escolà-Gil, Josep Julve, Gemma Llaverias, Mireia Urpi-Sarda, Reija Silvennoinen, Miriam Lee-Rueckert, Cristina Andres-Lacueva, Francisco Blanco-Vaca

Research output: Contribution to journalArticleResearchpeer-review

8 Citations (Scopus)

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. © 2013 Mosby, Inc. All rights reserved.
Original languageEnglish
Pages (from-to)110-117
JournalTranslational Research
Volume161
Issue number2
DOIs
Publication statusPublished - 1 Jan 2013

Keywords

  • ABC
  • adenosine triphosphate-binding cassette transporter
  • apo
  • apolipoprotein
  • cholesterol 7 alpha-hydroxylase
  • CYP7A1
  • HDL
  • high-density lipoprotein
  • liver X receptor
  • LXR
  • RCT
  • reverse cholesterol transport
  • scavenger receptor class-BI
  • SIRT1
  • SR-BI

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