PPARγ is required for the differentiation of adipose tissue in vivo and in vitro

被引:1737
作者
Rosen, ED
Sarraf, P
Troy, AE
Bradwin, G
Moore, K
Milstone, DS
Spiegelman, BM [1 ]
Mortensen, RM
机构
[1] Harvard Univ, Sch Med, Dana Farber Canc Inst, Cambridge, MA 02138 USA
[2] Harvard Univ, Sch Med, Dept Cell Biol, Cambridge, MA 02138 USA
[3] Brigham & Womens Hosp, Dept Med, Div Endocrine Hypertens, Boston, MA 02115 USA
[4] Brigham & Womens Hosp, Div Vasc Res, Boston, MA 02115 USA
[5] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA
[6] Massachusetts Gen Hosp, Lipid Metab Unit, Boston, MA 02114 USA
关键词
D O I
10.1016/S1097-2765(00)80211-7
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
The process of adipogenesis is known to involve the interplay of several transcription factors. Activation of one of these factors, the nuclear hormone receptor PPAR gamma, is known to promote fat cell differentiation in vitro. Whether PPAR gamma is required for this process in vivo has remained an open question because a viable loss-of-function model for PPAR gamma has been lacking. We demonstrate here that mice chimeric for wild-type and PPAR gamma null cells show little or no contribution of null cells to adipose tissue, whereas most other organs examined do not require PPAR gamma for proper development. In vitro, the differentiation of ES cells into fat is shown to be dependent on PPAR gamma gene dosage. These data provide direct evidence that PPAR gamma is essential for the formation of fat.
引用
收藏
页码:611 / 617
页数:7
相关论文
共 27 条
  • [21] Differentiation and reversal of malignant changes in colon cancer through PPARγ
    Sarraf, P
    Mueller, E
    Jones, D
    King, FJ
    DeAngelo, DJ
    Partridge, JB
    Holden, SA
    Chen, LB
    Singer, S
    Fletcher, C
    Spiegelman, BM
    [J]. NATURE MEDICINE, 1998, 4 (09) : 1046 - 1052
  • [22] Loss-of-function mutations in PPARγ associated with human colon cancer
    Sarraf, P
    Mueller, E
    Smith, WM
    Wright, HM
    Kum, JB
    Aaltonen, LA
    de la Chapelle, A
    Spiegelman, BM
    Eng, C
    [J]. MOLECULAR CELL, 1999, 3 (06) : 799 - 804
  • [23] MPPAR-GAMMA-2 - TISSUE-SPECIFIC REGULATOR OF AN ADIPOCYTE ENHANCER
    TONTONOZ, P
    HU, E
    GRAVES, RA
    BUDAVARI, AI
    SPIEGELMAN, BM
    [J]. GENES & DEVELOPMENT, 1994, 8 (10) : 1224 - 1234
  • [24] STIMULATION OF ADIPOGENESIS IN FIBROBLASTS BY PPAR-GAMMA-2, A LIPID-ACTIVATED TRANSCRIPTION FACTOR
    TONTONOZ, P
    HU, ED
    SPIEGELMAN, BM
    [J]. CELL, 1994, 79 (07) : 1147 - 1156
  • [25] PPARγ promotes monocyte/macrophage differentiation and uptake of oxidized LDL
    Tontonoz, P
    Nagy, L
    Alvarez, JGA
    Thomazy, VA
    Evans, RM
    [J]. CELL, 1998, 93 (02) : 241 - 252
  • [26] Cross-regulation of C/EBPα and PPARγ controls the transcriptional pathway of adipogenesis and insulin sensitivity
    Wu, ZD
    Rosen, ED
    Brun, R
    Hauser, S
    Adelmant, G
    Troy, AE
    McKeon, C
    Darlington, GJ
    Spiegelman, BM
    [J]. MOLECULAR CELL, 1999, 3 (02) : 151 - 158
  • [27] CASCADE REGULATION OF TERMINAL ADIPOCYTE DIFFERENTIATION BY 3 MEMBERS OF THE C/EBP FAMILY OF LEUCINE-ZIPPER PROTEINS
    YEH, WC
    CAO, ZD
    CLASSON, M
    MCKNIGHT, SL
    [J]. GENES & DEVELOPMENT, 1995, 9 (02) : 168 - 181