G protein-coupled receptor 12 deficiency results in dyslipidemia and obesity in mice

被引:31
作者
Bjursell, Mikael
Gerdin, Anna-Karin
Jonsson, Marie
Surve, Vikas V.
Svensson, Lennart
Huang, Xu-Feng
Tornell, Jan
Bohlooly-Y, Mohammad [1 ]
机构
[1] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Physiol & Endocrinol, Gothenburg, Sweden
[2] AstraZeneca R&D, AstraZeneca Transgen & Comparat Genom, Molndal, Sweden
[3] AstraZeneca R&D, Dept Mol Pharmacol, Molndal, Sweden
[4] Univ Wollongong, Neurobiol Res Ctr Metab & Psychiat Disorders, Wollongong, NSW 2500, Australia
关键词
RER; neuronal expression; energy balance; energy expenditure; dyslipidemia; GPCR;
D O I
10.1016/j.bbrc.2006.07.090
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 has been proposed to be a result of an imbalance in the physiological system that controls and maintains the body energy homeostasis. Several G-protein coupled receptors (GPCRs) are involved in the regulation of energy homeostasis. To investigate the importance of GPCR12, mice deficient of this receptor (GPCR12 KO) were studied regarding metabolism. Expression of GPCR12 was found primarily in the limbic and sensory systems, indicating its possible involvement in motivation, emotion together with various autonomic functions, and sensory information processing. GPCR12 KO mice were found to have higher body weight, body fat mass, lower respiratory exchange ratio (RER), hepatic steatosis, and were dyslipidemic. Neither food intake nor energy in faeces was affected in the GPCR12 KO mice. However, lower energy expenditure was found in the GPCR12 KO mice, which may explain the obesity. In conclusion, GPCR12 is considered important for the energy balance since GPCR12 KO mice develop obesity and have lower energy expenditure. This may be important for future drugs that target this receptor. 0 (c) 2006 Elsevier Inc. All rights reserved.
引用
收藏
页码:359 / 366
页数:8
相关论文
共 29 条
  • [1] Blockade of cannabinoid receptors by SR141716 selectively increases Fos expression in rat mesocorticolimbic areas via reduced dopamine D2 function
    Alonso, R
    Voutsinos, B
    Fournier, M
    Labie, C
    Steinberg, R
    Souilhac, J
    Le Fur, G
    Soubrie, P
    [J]. NEUROSCIENCE, 1999, 91 (02) : 607 - 620
  • [2] Identification of temperature-sensitive neural circuits in mice using c-Fos expression mapping
    Bachtell, RK
    Tsivkovskaia, NO
    Ryabinin, AE
    [J]. BRAIN RESEARCH, 2003, 960 (1-2) : 157 - 164
  • [3] Importance of melanin-concentrating hormone receptor for the acute effects of ghrelin
    Bjursell, M
    Egecioglu, E
    Gerdin, AK
    Svensson, L
    Oscarsson, J
    Morgan, D
    Snaith, M
    Törnell, J
    Bohlooly-Y, M
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2005, 326 (04) : 759 - 765
  • [4] Molecular tinkering of G protein-coupled receptors: an evolutionary success
    Bockaert, J
    Pin, JP
    [J]. EMBO JOURNAL, 1999, 18 (07) : 1723 - 1729
  • [5] BOHLOOLY YM, 2005, DIABETES, V54
  • [6] Identification of signal transduction pathways used by orphan G protein-coupled receptors
    Bresnick, JN
    Skynner, HA
    Chapman, KL
    Jack, AD
    Zamiara, E
    Negulescu, P
    Beaumont, K
    Patel, S
    McAllister, G
    [J]. ASSAY AND DRUG DEVELOPMENT TECHNOLOGIES, 2003, 1 (02) : 239 - 249
  • [7] Cota D, 2003, J CLIN INVEST, V112, P423, DOI [10.1172/JCI200317725, 10.1172/JCI17725]
  • [8] Overexpression of the A1 adenosine receptor in adipose tissue protects mice from obesity-related insulin resistance
    Dong, Q
    Ginsberg, HN
    Erlanger, BF
    [J]. DIABETES OBESITY & METABOLISM, 2001, 3 (05) : 360 - 366
  • [9] Drug discovery: A historical perspective
    Drews, J
    [J]. SCIENCE, 2000, 287 (5460) : 1960 - 1964
  • [10] Growth hormone receptor deficiency results in blunted ghrelin feeding response, obesity, and hypolipidemia in mice
    Egecioglu, E
    Bjursell, M
    Ljungberg, A
    Dickson, SL
    Kopchick, JJ
    Bergström, G
    Svensson, L
    Oscarsson, J
    Törnell, J
    Bohlooly-Y, M
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2006, 290 (02): : E317 - E325