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HSP47 levels determine the degree of body adiposity

Author

Listed:
  • Jihoon Shin

    (Osaka University
    Osaka University
    Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School)

  • Shinichiro Toyoda

    (Osaka University)

  • Yosuke Okuno

    (Osaka University)

  • Reiko Hayashi

    (Osaka University)

  • Shigeki Nishitani

    (Osaka University)

  • Toshiharu Onodera

    (Osaka University
    The University of Texas Southwestern Medical Center)

  • Haruyo Sakamoto

    (Osaka University)

  • Shinya Ito

    (Faculty of Life Sciences, Kyoto Sangyo University)

  • Sachiko Kobayashi

    (Osaka University)

  • Hirofumi Nagao

    (Osaka University)

  • Shunbun Kita

    (Osaka University
    Osaka University)

  • Michio Otsuki

    (Osaka University
    Tokyo Women’s Medical University)

  • Atsunori Fukuhara

    (Osaka University
    Osaka University)

  • Kazuhiro Nagata

    (Kyoto Sangyo University
    JT Biohistory Research Hall)

  • Iichiro Shimomura

    (Osaka University)

Abstract

Adiposity varies among individuals with the influence of diverse physiological, pathological, environmental, hormonal, and genetic factors, but a unified molecular basis remains elusive. Here, we identify HSP47, a collagen-specific chaperone, as a key determinant of body adiposity. HSP47 expression is abundant in adipose tissue; increased with feeding, overeating, and obesity; decreased with fasting, exercise, calorie restriction, bariatric surgery, and cachexia; and correlated with fat mass, BMI, waist, and hip circumferences. Insulin and glucocorticoids, respectively, up- and down-regulate HSP47 expression. In humans, the increase of HSP47 gene expression by its intron or synonymous variants is associated with higher body adiposity traits. In mice, the adipose-specific knockout or pharmacological inhibition of HSP47 leads to lower body adiposity compared to the control. Mechanistically, HSP47 promotes collagen dynamics in the folding, secretion, and interaction with integrin, which activates FAK signaling and preserves PPARγ protein from proteasomal degradation, partly related to MDM2. The study highlights the significance of HSP47 in determining the amount of body fat individually and under various circumstances.

Suggested Citation

  • Jihoon Shin & Shinichiro Toyoda & Yosuke Okuno & Reiko Hayashi & Shigeki Nishitani & Toshiharu Onodera & Haruyo Sakamoto & Shinya Ito & Sachiko Kobayashi & Hirofumi Nagao & Shunbun Kita & Michio Otsuk, 2023. "HSP47 levels determine the degree of body adiposity," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43080-x
    DOI: 10.1038/s41467-023-43080-x
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    References listed on IDEAS

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