5.9
CiteScore
5.9
Impact Factor
Volume 39 Issue 4
Apr.  2012
Turn off MathJax
Article Contents

Imipramine Inhibits Adipogenic Differentiation in Both 3T3-L1 Preadipocytes and Mouse Marrow Stromal Cells

doi: 10.1016/j.jgg.2012.03.003
More Information
  • Corresponding author: E-mail address: caigp@sz.tsinghua.edu.cn (Guoping Cai); E-mail address: bhmyang@cityu.edu.hk (Mengsu Yang)
  • Received Date: 2011-11-15
  • Accepted Date: 2012-03-19
  • Rev Recd Date: 2012-03-15
  • Available Online: 2012-03-27
  • Publish Date: 2012-04-20
  • Imipramine (IM) has been widely used clinically for the treatment of mental disorders. Its actions on tissues or organs other than the nervous system also need to be understood for its proper clinical use. In this study, the effects of IM on adipogenic differentiation in both 3T3-L1 preadipocytes and mouse marrow stromal cells (MSCs) were investigated. The results showed that fewer adipocytic cells were developed from 3T3-L1 preadipocytes in the presence of 0.001 to 1μmol/L of IM as compared to control. Similar inhibitory effect was also observed in mouse MSCs. The decrease in the formation of adipocytes was accompanied with significant down-regulation at mRNA expression of the early adipogenic transcription factor, peroxisome proliferator-activated receptor γ2 (PPARγ2). Western blot analysis further revealed that the protein expression of PPARγ2 was reduced markedly in cells treated with IM at concentrations of 0.01, 0.1 and 1μmol/L, suggesting that the suppression on PPARγ2 was involved in IM's inhibition on MSCs adipogenesis. Moreover, IM at the above concentrations could stimulate the mRNA expression of β2-adrenergic receptor (AR) and β3-AR, which implicated that the effect of IM on adipogenic differentiation was partially mediated by β-ARs. Our results demonstrated for the first time that the conventional antidepressive imipramine exerts accompanied inhibitory effect on adipocyte formation, which may have possible clinical implications.
  • Present address: College of Life Sciences, Shandong Agricultural University, Taian, Shangdong 271018, China.
  • loading
  • [1]
    Bachman, E.S., Dhillon, H., Zhang, C.Y. et al. βAR signaling required for diet-induced thermogenesis and obesity resistance Science, 297 (2002),pp. 843-845
    [2]
    Bertile, F., Criscuolo, F., Oudart, H. et al. Differences in the expression of lipolytic-related genes in rat white adipose tissues Biochem. Biophy. Res. Commun., 307 (2003),pp. 540-546
    [3]
    Bradford, B.L. PPARγ: an essential regulator of adipogenesis and modulator of fat cell function Cell, 99 (1999),pp. 239-242
    [4]
    Breslow, M.J., An, Y., Berkowitz, D.E. Beta-3 adrenoceptor (beta-3 AR) expression in leptin treated ob/ob mice Life Sci., 61 (1997),pp. 59-64
    [5]
    Carmen, G.Y., Víctor, S.M. Signalling mechanisms regulating lipolysis Cell. Signal., 18 (2006),pp. 401-408
    [6]
    Cheetham, S.C., Jackson, H.C., Vickers, S.P. et al. Novel targets for the treatment of obesity: a review of progress Drug Discov. Today Ther. Strat., 1 (2004),pp. 227-235
    [7]
    Dominici, M., Hofmann, T.J., Horwitz, E.M. Bone marrow mesenchymal cells: biological properties and clinical applications J. Biol. Regul. Homeost. Agents, 15 (2001),pp. 28-37
    [8]
    Fasshauer, M., Klein, J., Neumann, S. et al. FEBS Lett., 507 (2001),pp. 142-146
    [9]
    Fischbach, C., Spruss, T., Weiser, B. et al. Exp. Cell Res., 300 (2004),pp. 54-64
    [10]
    Fontana, E., Morin, N., Prévot, D. et al. Effects of octopamine on lipolysis, glucose transport and amine oxidation in mammalian fat cells Comp. Biochem. Physiol. C, 125 (2000),pp. 33-44
    [11]
    Grønning, L.M., Baillie, G.S., Cederberg, A. et al. Reduced PDE4 expression and activity contributes to enhanced catecholamine-induced cAMP accumulation in adipocytes from FOXC2 transgenic mice FEBS Lett., 580 (2006),pp. 4126-4130
    [12]
    Heydendael, W., Jacobson, L. Differential effects of imipramine and phenelzine on corticosteroid receptor gene expression in mouse brain: potential relevance to antidepressant response Brain Res., 1238 (2008),pp. 93-107
    [13]
    Lafontaine, J.A., Day, R.F., Dibrino, J. et al. Discovery of potent and orally bioavailable heterocycle-based β3-adrenergic receptor agonists, potential therapeutics for the treatment of obesity Bioorg. Med. Chem. Lett., 17 (2007),pp. 5245-5250
    [14]
    Li, H., Fong, C., Chen, Y. et al. Beta-adrenergic signals regulate adipogenesis of mouse mesenchymal stem cells via cAMP/PKA pathway Mol. Cell. Endocrinol., 323 (2010),pp. 201-207
    [15]
    Li, X., Cui, Q., Kao, C. et al. Lovastatin inhibits adipogenic and stimulates osteogenic differentiation by suppressing PPARγ2 and increasing Cbfa1/Runx2 expression in bone marrow mesenchymal cell cultures Bone, 33 (2003),pp. 652-659
    [16]
    Mills, S. Beta-adrenergic receptor subtypes mediating lipolysis in porcine adipocytes. Studies with RL-37344, a putative β3-adrenergic agonist Comp. Biochem. Physiol. C, 126 (2000),pp. 11-20
    [17]
    Rickard, D.J., Wang, F.L., Rodriguez-Rojas, A.M. et al. Intermittent treatment with parathyroid hormone (PTH) as well as a non-peptide small molecule agonist of the PTH1 receptor inhibits adipocyte differentiation in human bone marrow stromal cells Bone, 39 (2006),pp. 1361-1372
    [18]
    Robert, R., Tcheung, W.J., Rosenberg, L. et al. Treating thermally injured children suffering symptoms of acute stress with imipramine and fluoxetine: a randomized, double-blind study Burns, 34 (2008),pp. 919-928
    [19]
    Yirmiya, R., Goshen, I., Bajayo, A. et al. Depression induces bone loss through stimulation of the sympathetic nervous system Proc. Natl. Acad. Sci. USA, 103 (2006),pp. 16876-16881
    [20]
    Zhou, H., Yang, X., Wang, N.L. et al. Tigogenin inhibits adipocytic differentiation and induces osteoblastic differentiation in mouse bone marrow stromal cells Mol. Cell. Endocrinol., 270 (2007),pp. 17-22
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Article Metrics

    Article views (71) PDF downloads (0) Cited by ()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return