Thermogenic adipocytes promote HDL turnover and reverse cholesterol transport

被引:117
作者
Bartelt, Alexander [1 ,2 ,3 ,4 ]
John, Clara [1 ]
Schaltenberg, Nicola [1 ]
Berbee, Jimmy F. P. [5 ,6 ]
Worthmann, Anna [1 ]
Cherradi, M. Lisa [1 ]
Schlein, Christian [1 ]
Piepenburg, Julia [1 ]
Boon, Mariette R. [5 ,6 ]
Rinninger, Franz [7 ]
Heine, Markus [1 ]
Toedter, Klaus [1 ]
Niemeier, Andreas [2 ]
Nilsson, Stefan K. [1 ,8 ]
Fischer, Markus [9 ]
Wijers, Sander L. [10 ]
Lichtenbelt, Wouter van Marken [10 ]
Scheja, Ludger [1 ]
Rensen, Patrick C. N.
Heeren, Joerg [1 ]
机构
[1] Univ Med Ctr Hamburg Eppendorf, Dept Biochem & Mol Cell Biol, Martinistr 52, D-20246 Hamburg, Germany
[2] Univ Med Ctr Hamburg Eppendorf, Dept Orthopaed, Martinistr 52, D-20246 Hamburg, Germany
[3] Harvard TH Chan Sch Publ Hlth, Dept Genet & Complex Dis, 665 Huntington Ave, Boston, MA 02115 USA
[4] Harvard TH Chan Sch Publ Hlth, Sabri Ulker Ctr, 665 Huntington Ave, Boston, MA 02115 USA
[5] Leiden Univ, Med Ctr, Dept Med, Div Endocrinol, POB 9600, NL-2300 RC Leiden, Netherlands
[6] Leiden Univ, Med Ctr, Dept Med, Einthoven Lab Expt Vasc Med, POB 9600, NL-2300 RC Leiden, Netherlands
[7] Univ Med Ctr Hamburg Eppendorf, Dept Internal Med 3, Martinistr 52, D-20246 Hamburg, Germany
[8] Umea Univ, Dept Med Biosci & Physiol Chem, S-90787 Umea, Sweden
[9] Univ Hamburg, Inst Food Chem, Hamburg Sch Food Sci, Grindelallee 117, D-20146 Hamburg, Germany
[10] Maastricht Univ, Med Ctr, Dept Human Biol, NUTRIM Sch Nutr Toxicol & Metab, NL-6200 MD Maastricht, Netherlands
关键词
BROWN ADIPOSE-TISSUE; HIGH-DENSITY-LIPOPROTEIN; APOLIPOPROTEIN-A-I; SCAVENGER RECEPTOR; COLD-EXPOSURE; ADAPTIVE THERMOGENESIS; CELLULAR CHOLESTEROL; ENERGY-EXPENDITURE; PLASMA-MEMBRANE; FAT DEVELOPMENT;
D O I
10.1038/ncomms15010
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
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页数:10
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