HSP47 levels determine the degree of body adiposity

Jihoon Shin (), Shinichiro Toyoda, Yosuke Okuno, Reiko Hayashi, Shigeki Nishitani, Toshiharu Onodera, Haruyo Sakamoto, Shinya Ito, Sachiko Kobayashi, Hirofumi Nagao, Shunbun Kita, Michio Otsuki, Atsunori Fukuhara, Kazuhiro Nagata and Iichiro Shimomura
Additional contact information
Jihoon Shin: Osaka University
Shinichiro Toyoda: Osaka University
Yosuke Okuno: Osaka University
Reiko Hayashi: Osaka University
Shigeki Nishitani: Osaka University
Toshiharu Onodera: Osaka University
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
Michio Otsuki: Osaka University
Atsunori Fukuhara: Osaka University
Kazuhiro Nagata: Kyoto Sangyo University
Iichiro Shimomura: Osaka University

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-43080-x

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