Thermogenic adipocytes promote HDL turnover and reverse cholesterol transport

Alexander Bartelt*, Clara John, Nicola Schaltenberg, Jimmy F. P. Berbee, Anna Worthmann, M. Lisa Cherradi, Christian Schlein, Julia Piepenburg, Mariette R. Boon, Franz Rinninger, Markus Heine, Klaus Toedter, Andreas Niemeier, Stefan K. Nilsson, Markus Fischer, Sander L. Wijers, Wouter van Marken Lichtenbelt, Ludger Scheja, Patrick C. N. Rensen, Joerg Heeren*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

88 Citations (Web of Science)

Abstract

Brown and beige adipocytes combust nutrients for thermogenesis and through their metabolic activity decrease pro-atherogenic remnant lipoproteins in hyperlipidemic mice. However, whether the activation of thermogenic adipocytes affects the metabolism and anti-atherogenic properties of high-density lipoproteins (HDL) is unknown. Here, we report a reduction in atherosclerosis in response to pharmacological stimulation of thermogenesis linked to increased HDL levels in APOE(star)3-Leiden. CETP mice. Both cold-induced and pharmacological thermogenic activation enhances HDL remodelling, which is associated with specific lipidomic changes in mouse and human HDL. Furthermore, thermogenic stimulation promotes HDL-cholesterol clearance and increases macrophage-to-faeces reverse cholesterol transport in mice. Mechanistically, we show that intravascular lipolysis by adipocyte lipoprotein lipase and hepatic uptake of HDL by scavenger receptor B-I are the driving forces of HDL-cholesterol disposal in liver. Our findings corroborate the notion that high metabolic activity of thermogenic adipocytes confers atheroprotective properties via increased systemic cholesterol flux through the HDL compartment.

Original languageEnglish
Article number15010
Number of pages10
JournalNature Communications
Volume8
DOIs
Publication statusPublished - 19 Apr 2017

Keywords

  • BROWN ADIPOSE-TISSUE
  • HIGH-DENSITY-LIPOPROTEIN
  • TYPE-2 DIABETES-MELLITUS
  • APOLIPOPROTEIN-A-I
  • CARDIOVASCULAR-DISEASE
  • SCAVENGER RECEPTOR
  • COLD-EXPOSURE
  • ADAPTIVE THERMOGENESIS
  • CELLULAR CHOLESTEROL
  • ENERGY-EXPENDITURE

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