Format

Send to

Choose Destination
Nutrients. 2019 Feb 23;11(2). pii: E463. doi: 10.3390/nu11020463.

Effects of Pharmacological Thermogenic Adipocyte Activation on Metabolism and Atherosclerotic Plaque Regression.

Author information

1
Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany. a.worthmann@uke.de.
2
Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany. c.schlein@uke.de.
3
Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany. c.schlein@uke.de.
4
Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany. c.schlein@uke.de.
5
Department of Medicine, Division of Endocrinology and Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. J.F.P.Berbee@lumc.nl.
6
Department of Medicine, Division of Endocrinology and Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. P.C.N.Rensen@lumc.nl.
7
Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany. heeren@uke.de.
8
Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany. alexander.bartelt@med.uni-muenchen.de.
9
Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University, 81377 Munich, Germany. alexander.bartelt@med.uni-muenchen.de.
10
German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, 80336 Munich, Germany. alexander.bartelt@med.uni-muenchen.de.

Abstract

Thermogenic adipocytes burn nutrients in order to produce heat. Upon activation, brown adipose tissue (BAT) clears vast amounts of lipids and glucose from the circulation and thus substantially lowers plasma lipid levels. As a consequence, BAT activation protects from the development of atherosclerosis. However, it is unclear if pharmacologic activation of BAT can be exploited therapeutically to reduce plaque burden in established atherosclerotic disease. Here we study the impact of thermogenic adipose tissues on plaque regression in a mouse model of atherosclerosis. Thermogenic adipocytes in atherosclerotic low-density lipoprotein (LDL) receptor (LDLR)-deficient mice were pharmacologically activated by dietary CL316,243 (CL) treatment for 4 weeks and the outcomes on metabolically active tissues, plasma lipids and atherosclerosis were analyzed. While the chronic activation of thermogenic adipocytes reduced adiposity, increased browning of white adipose tissue (WAT), altered liver gene expression, and reduced plasma triglyceride levels, atherosclerotic plaque burden remained unchanged. Our findings suggest that despite improving adiposity and plasma triglycerides, pharmacologic activation of thermogenic adipocytes is not able to reverse atherosclerosis in LDLR-deficient mice.

KEYWORDS:

LDLR; atherosclerosis; brown adipose tissue; browning; cholesterol; thermogenesis; triglyceride

PMID:
30813320
DOI:
10.3390/nu11020463
Free full text

Supplemental Content

Full text links

Icon for Multidisciplinary Digital Publishing Institute (MDPI)
Loading ...
Support Center