Cold-induced activation of brown adipose tissue and adipose angiogenesis in mice

被引:175
作者
Lim, Sharon [1 ]
Honek, Jennifer [1 ]
Xue, Yuan [1 ]
Seki, Takahiro [1 ]
Cao, Ziquan [2 ]
Andersson, Patrik [1 ]
Yang, Xiaojuan [1 ]
Hosaka, Kayoko [1 ]
Cao, Yihai [1 ,2 ]
机构
[1] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden
[2] Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden
基金
欧洲研究理事会; 瑞典研究理事会;
关键词
OBESITY; ADIPOCYTES; ABLATION; FOXC2;
D O I
10.1038/nprot.2012.013
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Exposure of humans and rodents to cold activates thermogenic activity in brown adipose tissue (BAT). This protocol describes a mouse model to study the activation of BAT and angiogenesis in adipose tissues by cold acclimation. After a 1-week exposure to 4 degrees C, adult C57BL/6 mice show an obvious transition from subcutaneous white adipose tissue (WAT) into brown-like adipose tissue (BRITE). The BRITE phenotype persists after continuous cold exposure, and by the end of week 5 BRITE contains a high number of uncoupling protein-1-positive mitochondria, a characteristic feature of BAT. During the transition from WAT into BRITE, the vascular density is markedly increased owing to the activation of angiogenesis. In BAT, cold exposure stimulates thermogenesis by increasing the mitochondrial content and metabolic rate. BAT and the increased metabolic rate result in a lean phenotype. This protocol provides an outstanding opportunity to study the molecular mechanisms that control adipose mass.
引用
收藏
页码:606 / 615
页数:10
相关论文
共 15 条
[1]   Angiogenesis modulates adipogenesis and obesity [J].
Cao, Yihai .
JOURNAL OF CLINICAL INVESTIGATION, 2007, 117 (09) :2362-2368
[2]   Adipose tissue angiogenesis as a therapeutic target for obesity and metabolic diseases [J].
Cao, Yihai .
NATURE REVIEWS DRUG DISCOVERY, 2010, 9 (02) :107-115
[3]   FOXC2 is a winged helix gene that counteracts obesity, hypertriglyceridemia, and diet-induced insulin resistance [J].
Cederberg, A ;
Gronning, LM ;
Ahrén, B ;
Taskén, K ;
Carlsson, P ;
Enerbäck, S .
CELL, 2001, 106 (05) :563-573
[4]   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
[5]   UCP1 Ablation Induces Obesity and Abolishes Diet-induced Thermogenesis in Mice Exempt from Thermal Stress by Living at Thermoneutrality [J].
Feldmann, Helena M. ;
Golozoubova, Valeria ;
Cannon, Barbara ;
Nedergaard, Jan .
CELL METABOLISM, 2009, 9 (02) :203-209
[6]   Adipocyte/macrophage fatty acid-binding proteins contribute to metabolic deterioration through actions in both macrophages and adipocytes in mice [J].
Furuhashi, Masato ;
Fucho, Raquel ;
Gorgun, Cem Z. ;
Tuncman, Guerol ;
Cao, Haiming ;
Hotamisligil, Goekhan S. .
JOURNAL OF CLINICAL INVESTIGATION, 2008, 118 (07) :2640-2650
[7]  
Lichtenbelt WDV, 2009, NEW ENGL J MED, V360, P1500, DOI 10.1056/NEJMoa0808718
[8]   DEVELOPMENT OF OBESITY IN TRANSGENIC MICE AFTER GENETIC ABLATION OF BROWN ADIPOSE-TISSUE [J].
LOWELL, BB ;
SSUSULIC, V ;
HAMANN, A ;
LAWITTS, JA ;
HIMMSHAGEN, J ;
BOYER, BB ;
KOZAK, LP ;
FLIER, JS .
NATURE, 1993, 366 (6457) :740-742
[9]   The Changed Metabolic World with Human Brown Adipose Tissue: Therapeutic Visions [J].
Nedergaard, Jan ;
Cannon, Barbara .
CELL METABOLISM, 2010, 11 (04) :268-272
[10]   Chronic Peroxisome Proliferator-activated Receptor γ (PPARγ) Activation of Epididymally Derived White Adipocyte Cultures Reveals a Population of Thermogenically Competent, UCP1-containing Adipocytes Molecularly Distinct from Classic Brown Adipocytes [J].
Petrovic, Natasa ;
Walden, Tomas B. ;
Shabalina, Irina G. ;
Timmons, James A. ;
Cannon, Barbara ;
Nedergaard, Jan .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285 (10) :7153-7164