title: Resveratrol administration or SIRT1 overexpression does not increase LXR signaling and macrophage-to-feces reverse cholesterol transport in vivo.
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.
authors.affiliation: IIB Sant Pau, Barcelona, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas, CIBERDEM, Barcelona, Spain. jescola@santpau.cat
authors.forename: Joan Carles
authors.initials: JC
authors.lastname: Escolà-Gil
authors.forename: Josep
authors.initials: J
authors.lastname: Julve
authors.forename: Gemma
authors.initials: G
authors.lastname: Llaverias
authors.forename: Mireia
authors.initials: M
authors.lastname: Urpi-Sarda
authors.forename: Reija
authors.initials: R
authors.lastname: Silvennoinen
authors.forename: Miriam
authors.initials: M
authors.lastname: Lee-Rueckert
authors.forename: Cristina
authors.initials: C
authors.lastname: Andres-Lacueva
authors.forename: Francisco
authors.initials: F
authors.lastname: Blanco-Vaca
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D005243:Feces / Q000737:chemistry; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D000071518:Liver X Receptors; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D057093:Orphan Nuclear Receptors / Q000378:metabolism*; D000077185:Resveratrol; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000235:genetics* / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
chemical_list: D000975:Antioxidants; D002784:Cholesterol; D006845:Hydrocarbons, Fluorinated; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D000077185:Resveratrol; D056564:Sirtuin 1; D013267:Stilbenes; D013449:Sulfonamides; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides; C470545:Sirt1 protein, mouse