Thermogenic adipocytes promote HDL turnover and reverse cholesterol transport

Alexander Bartelt (), Clara John, Nicola Schaltenberg, Jimmy F. P. Berbée, Anna Worthmann, M. Lisa Cherradi, Christian Schlein, Julia Piepenburg, Mariëtte 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 and Joerg Heeren ()
Additional contact information
Alexander Bartelt: University Medical Center Hamburg-Eppendorf
Clara John: University Medical Center Hamburg-Eppendorf
Nicola Schaltenberg: University Medical Center Hamburg-Eppendorf
Jimmy F. P. Berbée: Leiden University Medical Center
Anna Worthmann: University Medical Center Hamburg-Eppendorf
M. Lisa Cherradi: University Medical Center Hamburg-Eppendorf
Christian Schlein: University Medical Center Hamburg-Eppendorf
Julia Piepenburg: University Medical Center Hamburg-Eppendorf
Mariëtte R. Boon: Leiden University Medical Center
Franz Rinninger: University Medical Center Hamburg-Eppendorf
Markus Heine: University Medical Center Hamburg-Eppendorf
Klaus Toedter: University Medical Center Hamburg-Eppendorf
Andreas Niemeier: University Medical Center Hamburg-Eppendorf
Stefan K. Nilsson: University Medical Center Hamburg-Eppendorf
Markus Fischer: Hamburg School of Food Science, Institute of Food Chemistry, University of Hamburg
Sander L. Wijers: NUTRIM - School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center
Wouter van Marken Lichtenbelt: NUTRIM - School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center
Ludger Scheja: University Medical Center Hamburg-Eppendorf
Patrick C. N. Rensen: Leiden University Medical Center
Joerg Heeren: University Medical Center Hamburg-Eppendorf

Nature Communications, 2017, vol. 8, issue 1, 1-10

Abstract: 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*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.

Date: 2017
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DOI: 10.1038/ncomms15010

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