Thermogenic Adipocytes Promote HDL Turnover and Reverse Cholesterol Transport

Overview

Journal Nat Commun

Specialty Biology

Date 2017 Apr 20

PMID 28422089

Citations 72

Authors

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

Affiliations

Soon will be listed here.

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.

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