TY - JOUR
T1 - Atorvastatin accelerates clearance of lipoprotein remnants generated by activated brown fat to further reduce hypercholesterolemia and atherosclerosis
AU - Hoeke, Geerte
AU - Wang, Yanan
AU - van Dam, Andrea D.
AU - Mol, Isabel M.
AU - Gart, Eveline
AU - Klop, Henk G.
AU - van den Berg, Susan M.
AU - Pieterman, Elsbet H.
AU - Princen, Hans M. G.
AU - Groen, Albert K.
AU - Rensen, Patrick C. N.
AU - Berbée, Jimmy F. P.
AU - Boon, Mariëtte R.
PY - 2017
Y1 - 2017
N2 - Background and aims: Activation of brown adipose tissue (BAT) reduces both hyperlipidemia and atherosclerosis by increasing the uptake of triglyceride-derived fatty acids by BAT, accompanied by formation and clearance of lipoprotein remnants. We tested the hypothesis that the hepatic uptake of lipoprotein remnants generated by BAT activation would be accelerated by concomitant statin treatment, thereby further reducing hypercholesterolemia and atherosclerosis. Methods: APOE*3-Leiden. CETP mice were fed a Western-type diet and treated without or with the selective beta 3-adrenergic receptor (AR) agonist CL316,243 that activates BAT, atorvastatin (statin) or both. Results: beta 3-AR agonism increased energy expenditure as a result of an increased fat oxidation by activated BAT, which was not further enhanced by statin addition. Accordingly, statin treatment neither influenced the increased uptake of triglyceride-derived fatty acids from triglyceride-rich lipoprotein-like particles by BAT nor further lowered plasma triglyceride levels induced by beta 3-AR agonism. Statin treatment increased the hepatic uptake of the formed cholesterol-enriched remnants generated by beta 3-AR agonism. Consequently, statin treatment further lowered plasma cholesterol levels. Importantly, statin, in addition to beta 3-AR agonism, also further reduced the atherosclerotic lesion size as compared to beta 3-AR agonism alone, without altering lesion severity and composition. Conclusions: Statin treatment accelerates the hepatic uptake of remnants generated by BAT activation, thereby increasing the lipid-lowering and anti-atherogenic effects of BAT activation in an additive fashion. We postulate that, in clinical practice, combining statin treatment with BAT activation is a promising new avenue to combat hyperlipidemia and cardiovascular disease. (C) 2017 Elsevier B.V. All rights reserved
AB - Background and aims: Activation of brown adipose tissue (BAT) reduces both hyperlipidemia and atherosclerosis by increasing the uptake of triglyceride-derived fatty acids by BAT, accompanied by formation and clearance of lipoprotein remnants. We tested the hypothesis that the hepatic uptake of lipoprotein remnants generated by BAT activation would be accelerated by concomitant statin treatment, thereby further reducing hypercholesterolemia and atherosclerosis. Methods: APOE*3-Leiden. CETP mice were fed a Western-type diet and treated without or with the selective beta 3-adrenergic receptor (AR) agonist CL316,243 that activates BAT, atorvastatin (statin) or both. Results: beta 3-AR agonism increased energy expenditure as a result of an increased fat oxidation by activated BAT, which was not further enhanced by statin addition. Accordingly, statin treatment neither influenced the increased uptake of triglyceride-derived fatty acids from triglyceride-rich lipoprotein-like particles by BAT nor further lowered plasma triglyceride levels induced by beta 3-AR agonism. Statin treatment increased the hepatic uptake of the formed cholesterol-enriched remnants generated by beta 3-AR agonism. Consequently, statin treatment further lowered plasma cholesterol levels. Importantly, statin, in addition to beta 3-AR agonism, also further reduced the atherosclerotic lesion size as compared to beta 3-AR agonism alone, without altering lesion severity and composition. Conclusions: Statin treatment accelerates the hepatic uptake of remnants generated by BAT activation, thereby increasing the lipid-lowering and anti-atherogenic effects of BAT activation in an additive fashion. We postulate that, in clinical practice, combining statin treatment with BAT activation is a promising new avenue to combat hyperlipidemia and cardiovascular disease. (C) 2017 Elsevier B.V. All rights reserved
U2 - https://doi.org/10.1016/j.atherosclerosis.2017.10.030
DO - https://doi.org/10.1016/j.atherosclerosis.2017.10.030
M3 - Article
C2 - 29121499
SN - 0021-9150
VL - 267
SP - 116
EP - 126
JO - Atherosclerosis
JF - Atherosclerosis
ER -