Soluble LR11/SorLA represses thermogenesis in adipose tissue and correlates with BMI in humans

被引：48

作者：

Whittle, Andrew J. ^{[1
]}

Jiang, Meizi ^{[2
,3
]}

Peirce, Vivian ^{[1
]}

Relat, Joana ^{[4
,5
]}

Virtue, Sam ^{[1
]}

Ebinuma, Hiroyuki ^{[6
]}

Fukamachi, Isamu ^{[6
]}

Yamaguchi, Takashi ^{[7
]}

Takahashi, Mao ^{[8
]}

Murano, Takeyoshi ^{[2
]}

Tatsuno, Ichiro ^{[7
]}

Takeuchi, Masahiro ^{[9
]}

Nakaseko, Chiaki ^{[9
]}

Jin, Wenlong ^{[10
]}

Jin, Zhehu ^{[11
]}

Campbell, Mark ^{[1
]}

Schneider, Wolfgang J. ^{[12
]}

Vidal-Puig, Antonio ^{[1
,13
]}

Bujo, Hideaki ^{[2
,3
]}

机构：

[1] Univ Cambridge, Metab Res Labs, Wellcome Trust MRC Inst Metab Sci, Addenbrookes Hosp, Cambridge CB2 OQQ, England

[2] Toho Univ, Dept Clin Lab & Expt Res Med, Sakura Med Ctr, Sakura, Chiba 2858741, Japan

[3] Chiba Univ, Grad Sch Med, Dept Genome Res & Clin Applicat, Chiba 2608670, Japan

[4] Univ Barcelona, Dept Biochem & Mol Biol, Sch Pharm, E-08028 Barcelona, Spain

[5] IBUB, Barcelona 08028, Spain

[6] Sekisui Med Co Ltd, Tsukuba Res Inst, Ryugasaki 3010852, Japan

[7] Toho Univ, Ctr Diabet Endocrinol & Metab, Sakura Med Ctr, Sakura, Chiba 2858741, Japan

[8] Toho Univ, Cardiovasc Ctr, Sakura Med Ctr, Sakura, Chiba 2858741, Japan

[9] Chiba Univ Hosp, Dept Hematol, Chiba 2608677, Japan

[10] Yanbian Univ, Dept Endocrinol, Affiliated Hosp, Yanji 133000, Peoples R China

[11] Yanbian Univ, Dept Dermatol, Affiliated Hosp, Yanji 133000, Peoples R China

[12] Med Univ Vienna, Dept Med Biochem, Max F Perutz Labs, A-1030 Vienna, Austria

[13] Wellcome Trust Sanger Inst, Dept Cellular Genet, Cambridge CB10 1SA, England

来源：

NATURE COMMUNICATIONS | 2015年 / 6卷

基金：

奥地利科学基金会; 英国生物技术与生命科学研究理事会; 英国惠康基金;

关键词：

DIET-INDUCED THERMOGENESIS; SMOOTH-MUSCLE-CELLS; WHITE FAT; BROWN-FAT; ENERGY-EXPENDITURE; ADULT HUMANS; LR11; MICE; THERMONEUTRALITY; IDENTIFICATION;

D O I：

10.1038/ncomms9951

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：

Thermogenesis in brown adipose tissue (BAT) is an important component of energy expenditure in mammals. Recent studies have confirmed its presence and metabolic role in humans. Defining the physiological regulation of BAT is therefore of great importance for developing strategies to treat metabolic diseases. Here we show that the soluble form of the low-density lipoprotein receptor relative, LR11/SorLA (sLR11), suppresses thermogenesis in adipose tissue in a cell-autonomous manner. Mice lacking LR11 are protected from diet-induced obesity associated with an increased browning of white adipose tissue and hypermetabolism. Treatment of adipocytes with sLR11 inhibits thermogenesis via the bone morphogenetic protein/TGFb signalling pathway and reduces Smad phosphorylation. In addition, sLR11 levels in humans are shown to positively correlate with body mass index and adiposity. Given the need for tight regulation of a tissue with a high capacity for energy wastage, we propose that LR11 plays an energy conserving role that is exaggerated in states of obesity.

引用

页数：12

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