TY - JOUR
T1 - Resveratrol administration or SIRT1 overexpression does not increase LXR signaling and macrophage-to-feces reverse cholesterol transport in vivo
AU - Escolà-Gil, Joan Carles
AU - Julve, Josep
AU - Llaverias, Gemma
AU - Urpi-Sarda, Mireia
AU - Silvennoinen, Reija
AU - Lee-Rueckert, Miriam
AU - Andres-Lacueva, Cristina
AU - Blanco-Vaca, Francisco
PY - 2013/1/1
Y1 - 2013/1/1
N2 - 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.
AB - 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.
KW - ABC
KW - adenosine triphosphate-binding cassette transporter
KW - apo
KW - apolipoprotein
KW - cholesterol 7 alpha-hydroxylase
KW - CYP7A1
KW - HDL
KW - high-density lipoprotein
KW - liver X receptor
KW - LXR
KW - RCT
KW - reverse cholesterol transport
KW - scavenger receptor class-BI
KW - SIRT1
KW - SR-BI
U2 - 10.1016/j.trsl.2012.10.008
DO - 10.1016/j.trsl.2012.10.008
M3 - Article
VL - 161
SP - 110
EP - 117
JO - Translational Research
JF - Translational Research
SN - 1931-5244
IS - 2
ER -