[HTML][HTML] Thermogenic adipocytes promote HDL turnover and reverse cholesterol transport

A Bartelt, C John, N Schaltenberg, JFP Berbée… - Nature …, 2017 - nature.com
A Bartelt, C John, N Schaltenberg, JFP Berbée, A Worthmann, ML Cherradi, C Schlein
Nature communications, 2017nature.com
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 …
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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