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Mechanical Stretching and Signaling Pathways in Adipogenesis

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The Mechanobiology of Obesity and Related Diseases

Part of the book series: Studies in Mechanobiology, Tissue Engineering and Biomaterials ((SMTEB,volume 16))

Abstract

Adipogenesis is a fundamental process to develop adipose tissues via commitment of mesenchymal stem cells (MSCs) to direction of preadipocytes and production of terminally differentiated lipid-laden adipocytes. While adipose tissues play important roles for energy and metabolic homeostasis in our body, dysregulated adiposities become considerable risk factors for various metabolic and cardiovascular diseases. In view of both preventive and therapeutic aspects, clinical interventions have been mostly directed at control of adiposity such as weight control by improved balance of calorie intake and energy expenditure. Physical exercise has been considered to be an effective approach to improve the systemic energy balance; however, the effects of locally generated mechanical stress on adipose tissues that are directly or indirectly accessible by the exercise and/or massage had remained obscure. It has now become apparent that stretching and other mechanical stimuli activate various cellular signals, including matrix elasticity/stiffness and cytoskeletal control, extracellular matrix–integrin interaction, the extracellular signal-regulated protein kinase/mitogen activated protein kinase (ERK/MAPK), Rho–Rho-kinase pathway, tension-induced/inhibited proteins (TIPs), the cyclooxygenase pathway, and Wnt signaling; all of them are involved in the mechanotransduction pathways and have a significant influence on adipogenesis. The stretching shows bidirectional effects of either inhibition or stimulation on adipogenesis that is presumably depending on the strength, duration, and timing of mechanical inputs, as well as cellular statuses of differentiation. The ERK/MAPK plays a crucial role in the bidirectional outcomes, and other coexisting signals adjust and determine the commitment and adipogenic statuses of MSCs and preadipocytes. These results imply that the mechanical stimulation would modulate the adipose tissue functions through the bidirectional control of adipocyte renewal, adiposity, endocrine function of adipocytes, and fine-tuning of drug actions.

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Acknowledgments

The authors thank Paul Langman, Ph.D. for his critical comments, discussion and advice for this manuscript. This work was partly supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan (1996–1997, 1998–1999, 2005–2007, 2010–2012), a grant from the Shizuoka Research Institute (1999–2000), and Goto Research Grant of University of Shizuoka (2003–2004).

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The authors declare no competing financial interests.

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Authors and Affiliations

  1. Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Iwate Medical University, 2-1-1 Nishitokuta, Yahaba-cho, Shiwa-gun, Iwate, 028-3694, Japan

    Yoshiyuki Tanabe, Maki Tanji Saito & Koichi Nakayama

  2. The Professor Emeritus, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 054-8526, Japan

    Koichi Nakayama

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  1. Yoshiyuki Tanabe
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    Amit Gefen

  2. Dept. of Cell and Developmental Biology Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel

    Dafna Benayahu

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Tanabe, Y., Saito, M.T., Nakayama, K. (2013). Mechanical Stretching and Signaling Pathways in Adipogenesis. In: Gefen, A., Benayahu, D. (eds) The Mechanobiology of Obesity and Related Diseases. Studies in Mechanobiology, Tissue Engineering and Biomaterials, vol 16. Springer, Cham. https://doi.org/10.1007/8415_2013_169

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