Beige Adipocytes Are a Distinct Type of Thermogenic Fat Cell in Mouse and Human

被引:2733
作者
Wu, Jun [1 ,2 ]
Bostrom, Pontus [1 ,2 ]
Sparks, Lauren M. [3 ]
Ye, Li [1 ,2 ]
Choi, Jang Hyun [1 ,2 ]
Giang, An-Hoa [1 ,2 ]
Khandekar, Melin [1 ,2 ]
Virtanen, Kirsi A. [6 ]
Nuutila, Pirjo [6 ]
Schaart, Gert [4 ]
Huang, Kexin [7 ]
Tu, Hua [7 ]
Lichtenbelt, Wouter D. van Marken [3 ]
Hoeks, Joris [3 ]
Enerbaeck, Sven [5 ]
Schrauwen, Patrick [3 ]
Spiegelman, Bruce M. [1 ,2 ]
机构
[1] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA
[2] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02215 USA
[3] Maastricht Univ Med Ctr, NUTRIM Sch Nutr Toxicol & Metab, Dept Human Biol, NL-6229 ER Maastricht, Netherlands
[4] Maastricht Univ Med Ctr, NUTRIM Sch Nutr Toxicol & Metab, Dept Human Movement Sci, NL-6229 ER Maastricht, Netherlands
[5] Gothenburg Univ, Inst Biomed, S-40530 Gothenburg, Sweden
[6] Univ Turku, Turku PET Ctr, FI-20521 Turku, Finland
[7] Lakepharma Inc, Belmont, CA 94002 USA
关键词
BROWN ADIPOSE-TISSUE; WHITE FAT; TRANSCRIPTIONAL CONTROL; SKELETAL-MUSCLE; IN-VIVO; IDENTIFICATION; PROGENITORS; ACTIVATION; INDUCTION; OBESITY;
D O I
10.1016/j.cell.2012.05.016
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Brown fat generates heat via the mitochondrial uncoupling protein UCP1, defending against hypothermia and obesity. Recent data suggest that there are two distinct types of brown fat: classical brown fat derived from a myf-5 cellular lineage and UCP1-positive cells that emerge in white fat from a non-myf-5 lineage. Here, we report the isolation of "beige" cells from murine white fat depots. Beige cells resemble white fat cells in having extremely low basal expression of UCP1, but, like classical brown fat, they respond to cyclic AMP stimulation with high UCP1 expression and respiration rates. Beige cells have a gene expression pattern distinct from either white or brown fat and are preferentially sensitive to the polypeptide hormone irisin. Finally, we provide evidence that previously identified brown fat deposits in adult humans are composed of beige adipocytes. These data provide a foundation for studying this mammalian cell type with therapeutic potential.
引用
收藏
页码:366 / 376
页数:11
相关论文
共 39 条
[1]   Developmental Origins of the Adipocyte Lineage: New Insights from Genetics and Genomics Studies [J].
Billon, Nathalie ;
Dani, Christian .
STEM CELL REVIEWS AND REPORTS, 2012, 8 (01) :55-66
[2]   Cardiac natriuretic peptides act via p38 MAPK to induce the brown fat thermogenic program in mouse and human adipocytes [J].
Bordicchia, Marica ;
Liu, Dianxin ;
Amri, Ez-Zoubir ;
Ailhaud, Gerard ;
Dessi-Fulgheri, Paolo ;
Zhang, Chaoying ;
Takahashi, Nobuyuki ;
Sarzani, Riccardo ;
Collins, Sheila .
JOURNAL OF CLINICAL INVESTIGATION, 2012, 122 (03) :1022-1036
[3]   A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis [J].
Bostroem, Pontus ;
Wu, Jun ;
Jedrychowski, Mark P. ;
Korde, Anisha ;
Ye, Li ;
Lo, James C. ;
Rasbach, Kyle A. ;
Bostroem, Elisabeth Almer ;
Choi, Jang Hyun ;
Long, Jonathan Z. ;
Kajimura, Shingo ;
Zingaretti, Maria Cristina ;
Vind, Birgitte F. ;
Tu, Hua ;
Cinti, Saverio ;
Hojlund, Kurt ;
Gygi, Steven P. ;
Spiegelman, Bruce M. .
NATURE, 2012, 481 (7382) :463-U72
[4]   Adipocyte differentiation and transdifferentiation: Plasticity of the adipose organ [J].
Cinti, S .
JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION, 2002, 25 (10) :823-835
[5]   Learning new tricks from old dogs:: β-adrenergic receptors teach new lessons on firing up adipose tissue metabolism [J].
Collins, S ;
Cao, WH ;
Robidoux, J .
MOLECULAR ENDOCRINOLOGY, 2004, 18 (09) :2123-2131
[6]   Strain-specific response to beta(3)-adrenergic receptor agonist treatment of diet-induced obesity in mice [J].
Collins, S ;
Daniel, KW ;
Petro, AE ;
Surwit, RS .
ENDOCRINOLOGY, 1997, 138 (01) :405-413
[7]   Dietary fat interacts with QTLs controlling induction of Pgc-1α and Ucp1 during conversion of white to brown fat [J].
Coulter, AA ;
Bearden, CM ;
Liu, XT ;
Koza, RA ;
Kozak, LP .
PHYSIOLOGICAL GENOMICS, 2003, 14 (02) :139-147
[8]  
COUSIN B, 1992, J CELL SCI, V103, P931
[9]   Identification and Importance of Brown Adipose Tissue in Adult Humans. [J].
Cypess, Aaron M. ;
Lehman, Sanaz ;
Williams, Gethin ;
Tal, Ilan ;
Rodman, Dean ;
Goldfine, Allison B. ;
Kuo, Frank C. ;
Palmer, Edwin L. ;
Tseng, Yu-Hua ;
Doria, Alessandro ;
Kolodny, Gerald M. ;
Kahn, C. Ronald .
NEW ENGLAND JOURNAL OF MEDICINE, 2009, 360 (15) :1509-1517
[10]   FGF21 regulates PGC-1α and browning of white adipose tissues in adaptive thermogenesis [J].
Fisher, Ffolliott M. ;
Kleiner, Sandra ;
Douris, Nicholas ;
Fox, Elliott C. ;
Mepani, Rina J. ;
Verdeguer, Francisco ;
Wu, Jun ;
Kharitonenkov, Alexei ;
Flier, Jeffrey S. ;
Maratos-Flier, Eleftheria ;
Spiegelman, Bruce M. .
GENES & DEVELOPMENT, 2012, 26 (03) :271-281