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Tenomodulin promotes human adipocyte differentiation and beneficial visceral adipose tissue expansion

Author

Listed:
  • Ozlem Senol-Cosar

    (Program in Molecular Medicine, University of Massachusetts Medical School)

  • Rachel J. Roth Flach

    (Program in Molecular Medicine, University of Massachusetts Medical School)

  • Marina DiStefano

    (Program in Molecular Medicine, University of Massachusetts Medical School)

  • Anil Chawla

    (Program in Molecular Medicine, University of Massachusetts Medical School)

  • Sarah Nicoloro

    (Program in Molecular Medicine, University of Massachusetts Medical School)

  • Juerg Straubhaar

    (Program in Molecular Medicine, University of Massachusetts Medical School)

  • Olga T. Hardy

    (Touchstone Diabetes Center, The University of Texas Southwestern Medical Center)

  • Hye Lim Noh

    (Program in Molecular Medicine, University of Massachusetts Medical School
    University of Massachusetts Medical School)

  • Jason K. Kim

    (Program in Molecular Medicine, University of Massachusetts Medical School
    University of Massachusetts Medical School)

  • Martin Wabitsch

    (University Medical Center Ulm)

  • Philipp E. Scherer

    (Touchstone Diabetes Center, The University of Texas Southwestern Medical Center)

  • Michael P. Czech

    (Program in Molecular Medicine, University of Massachusetts Medical School)

Abstract

Proper regulation of energy storage in adipose tissue is crucial for maintaining insulin sensitivity and molecules contributing to this process have not been fully revealed. Here we show that type II transmembrane protein tenomodulin (TNMD) is upregulated in adipose tissue of insulin-resistant versus insulin-sensitive individuals, who were matched for body mass index (BMI). TNMD expression increases in human preadipocytes during differentiation, whereas silencing TNMD blocks adipogenesis. Upon high-fat diet feeding, transgenic mice overexpressing Tnmd develop increased epididymal white adipose tissue (eWAT) mass, and preadipocytes derived from Tnmd transgenic mice display greater proliferation, consistent with elevated adipogenesis. In Tnmd transgenic mice, lipogenic genes are upregulated in eWAT, as is Ucp1 in brown fat, while liver triglyceride accumulation is attenuated. Despite expanded eWAT, transgenic animals display improved systemic insulin sensitivity, decreased collagen deposition and inflammation in eWAT, and increased insulin stimulation of Akt phosphorylation. Our data suggest that TNMD acts as a protective factor in visceral adipose tissue to alleviate insulin resistance in obesity.

Suggested Citation

  • Ozlem Senol-Cosar & Rachel J. Roth Flach & Marina DiStefano & Anil Chawla & Sarah Nicoloro & Juerg Straubhaar & Olga T. Hardy & Hye Lim Noh & Jason K. Kim & Martin Wabitsch & Philipp E. Scherer & Mich, 2016. "Tenomodulin promotes human adipocyte differentiation and beneficial visceral adipose tissue expansion," Nature Communications, Nature, vol. 7(1), pages 1-13, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10686
    DOI: 10.1038/ncomms10686
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    Cited by:

    1. Jing Yan & Yuemei Zhang & Hairong Yu & Yicen Zong & Daixi Wang & Jiangfei Zheng & Li Jin & Xiangtian Yu & Caizhi Liu & Yi Zhang & Feng Jiang & Rong Zhang & Xiangnan Fang & Ting Xu & Mingyu Li & Jianzh, 2022. "GPSM1 impairs metabolic homeostasis by controlling a pro-inflammatory pathway in macrophages," Nature Communications, Nature, vol. 13(1), pages 1-22, December.

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