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Atorvastatin accelerates clearance of lipoprotein remnants generated by activated brown fat to further reduce hypercholesterolemia and atherosclerosis
- Publication Year :
- 2017
-
Abstract
- 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 β3-adrenergic receptor (AR) agonist CL316,243 that activates BAT, atorvastatin (statin) or both. Results β3-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 β3-AR agonism. Statin treatment increased the hepatic uptake of the formed cholesterol-enriched remnants generated by β3-AR agonism. Consequently, statin treatment further lowered plasma cholesterol levels. Importantly, statin, in addition to β3-AR agonism, also further reduced the atherosclerotic lesion size as compared to β3-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.
- Subjects :
- Mouse
Hypercholesterolemia
Drug potentiation
Biomedical Innovation
Brown adipose tissue
Triacylglycerol
5 [2 [[2 (3 chlorophenyl) 2 hydroxyethyl]amino]propyl] 1
Animal tissue
EELS - Earth
Life
Atorvastatin
Cholesterol metabolism
Lipid and lipoprotein metabolism
Animal model
cardiovascular diseases
Animal experiment
Western diet
Lipoprotein
Biology
High density lipoprotein cholesterol
Lipoprotein metabolism
Lipid liver level
Lipid composition
nutritional and metabolic diseases
Atherosclerosis
Fatty acid
Proprotein convertase 9
Lipid transport
Nonhuman
Environmental and Life Sciences
Lipid oxidation
Triacylglycerol blood level
Drug effect
2 dicarboxylic acid
Cholesterol
Cholesterol blood level
Lipid metabolism
3 benzodioxole 2
lipids (amino acids, peptides, and proteins)
Energy expenditure
Female
Gene expression
MHR - Metabolic Health Research
Controlled study
Healthy Living
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.dris...00893..3213271e687c72a6d9e0dd6371857028