PPARs and the complex journey to obesity

被引:1317
作者
Evans, RM [1 ]
Barish, GD
Wang, YX
机构
[1] Salk Inst Biol Studies, Howard Hughes Med Inst, Gene Express Lab, La Jolla, CA 92037 USA
[2] Univ Calif San Francisco, Dept Med, Div Endocrinol & Metab, San Francisco, CA 94121 USA
基金
美国国家卫生研究院;
关键词
D O I
10.1038/nm1025
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
Obesity and the related disorders of dyslipidemia and diabetes (components of syndrome X) have become global health epidemics. Over the past decade, the elucidation of key regulators of energy balance and insulin signaling have revolutionized our understanding of fat and sugar metabolism and their intimate link. The three 'lipid-sensing' peroxisome proliferator-activated receptors (PPAR-alpha, PPAR-gamma and PPAR-delta) exemplify this connection, regulating diverse aspects of lipid and glucose homeostasis, and serving as bona fide therapeutic targets. With molecular underpinnings now in place, new pharmacologic approaches to metabolic disease and new questions are emerging.
引用
收藏
页码:355 / 361
页数:7
相关论文
共 104 条
  • [1] Early neonatal death in mice homozygous for a null allele of the insulin receptor gene
    Accili, D
    Drago, J
    Lee, EJ
    Johnson, MD
    Cool, MH
    Salvatore, P
    Asico, LD
    Jose, PA
    Taylor, SI
    Westphal, H
    [J]. NATURE GENETICS, 1996, 12 (01) : 106 - 109
  • [2] A novel heterozygous mutation in peroxisome proliferator-activated receptor-γ gene in a patient with familial partial lipodystrophy
    Agarwal, AK
    Garg, A
    [J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2002, 87 (01) : 408 - 411
  • [3] Disruption of the uncoupling protein-2 gene in mice reveals a role in immunity and reactive oxygen species production
    Arsenijevic, D
    Onuma, H
    Pecqueur, C
    Raimbault, S
    Manning, BS
    Miroux, B
    Couplan, E
    Alves-Guerra, MC
    Goubern, M
    Surwit, R
    Bouillaud, F
    Richard, D
    Collins, S
    Ricquier, D
    [J]. NATURE GENETICS, 2000, 26 (04) : 435 - 439
  • [4] βAR signaling required for diet-induced thermogenesis and obesity resistance
    Bachman, ES
    Dhillon, H
    Zhang, CY
    Cinti, S
    Bianco, AC
    Kobilka, BK
    Lowell, BB
    [J]. SCIENCE, 2002, 297 (5582) : 843 - 845
  • [5] Effects of peroxisome proliferator-activated receptor δ on placentation, adiposity, and colorectal cancer
    Barak, Y
    Liao, D
    He, WM
    Ong, ES
    Nelson, MC
    Olefsky, JM
    Boland, R
    Evans, RM
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (01) : 303 - 308
  • [6] PPARγ is required for placental, cardiac, and adipose tissue development
    Barak, Y
    Nelson, MC
    Ong, ES
    Jones, YZ
    Ruiz-Lozano, P
    Chien, KR
    Koder, A
    Evans, RM
    [J]. MOLECULAR CELL, 1999, 4 (04) : 585 - 595
  • [7] Gut hormone PYY3-36 physiologically inhibits food intake
    Batterham, RL
    Cowley, MA
    Small, CJ
    Herzog, H
    Cohen, MA
    Dakin, CL
    Wren, AM
    Brynes, AE
    Low, MJ
    Ghatei, MA
    Cone, RD
    Bloom, SR
    [J]. NATURE, 2002, 418 (6898) : 650 - 654
  • [8] The adipocyte-secreted protein Acrp30 enhances hepatic insulin action
    Berg, AH
    Combs, TP
    Du, XL
    Brownlee, M
    Scherer, PE
    [J]. NATURE MEDICINE, 2001, 7 (08) : 947 - 953
  • [9] Distinct properties and advantages of a novel peroxisome proliferator-activated protein γ selective modulator
    Berger, JP
    Petro, AE
    Macnaul, KL
    Kelly, LJ
    Zhang, BB
    Richards, K
    Elbrecht, A
    Johnson, BA
    Zhou, GC
    Doebber, TW
    Biswas, C
    Parikh, M
    Sharma, N
    Tanen, MR
    Thompson, GM
    Ventre, J
    Adams, AD
    Mosley, R
    Surwit, RS
    Moller, DE
    [J]. MOLECULAR ENDOCRINOLOGY, 2003, 17 (04) : 662 - 676
  • [10] Extended longevity in mice lacking the insulin receptor in adipose tissue
    Blüher, M
    Kahn, BB
    Kahn, CR
    [J]. SCIENCE, 2003, 299 (5606) : 572 - 574