HSP47 levels determine the degree of body adiposity

Shin, Jihoon; Toyoda, Shinichiro; Okuno, Yosuke; Hayashi, Reiko; Nishitani, Shigeki; Onodera, Toshiharu; Sakamoto, Haruyo; Ito, Shinya; Kobayashi, Sachiko; Nagao, Hirofumi; Kita, Shunbun; Otsuki, Michio; Fukuhara, Atsunori; Nagata, Kazuhiro; Shimomura, Iichiro

doi:https://doi.org/10.1038/s41467-023-43080-x

HSP47 levels determine the degree of body adiposity

Shin, Jihoon; Toyoda, Shinichiro; Okuno, Yosuke et al.

Nature Communications, 2023, 14, 7319

Number of Access:1,764（2025-07-18 09:58 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/93378

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Title	HSP47 levels determine the degree of body adiposity
Creator	NRID 1000000813502 1000000813502 ORCID 0000-0003-1294-0238 0000-0003-1294-0238 researchmap permalink shinjihoon0209 shinjihoon0209 Scopus Author ID 56967386500 56967386500 CreatorName Shin, Jihoon
	CreatorName Toyoda, Shinichiro
	NRID 1000010534513 1000010534513 researchmap permalink wokuno wokuno Scopus Author ID 14525595700 14525595700 CreatorName Okuno, Yosuke
	CreatorName Hayashi, Reiko
	NRID 1000030889407 1000030889407 researchmap permalink sgknstn sgknstn CreatorName Nishitani, Shigeki
	CreatorName Onodera, Toshiharu
	CreatorName Sakamoto, Haruyo
	CreatorName Ito, Shinya
	NRID 1000080649111 1000080649111 researchmap permalink skkk skkk Scopus Author ID 56307169100 56307169100 CreatorName Kobayashi, Sachiko
	NRID 1000070983146 1000070983146 researchmap permalink Hirofumi_Nagao Hirofumi_Nagao ORCID 0009-0001-1261-4160 0009-0001-1261-4160 CreatorName Nagao, Hirofumi
	NRID 1000010746572 1000010746572 CreatorName Kita, Shunbun
	NRID 1000000403056 1000000403056 CreatorName Otsuki, Michio
	NRID 1000000437328 1000000437328 ORCID 0000-0002-6289-3778 0000-0002-6289-3778 researchmap permalink AtsuF AtsuF Scopus Author ID 7003835710 7003835710 CreatorName Fukuhara, Atsunori
	CreatorName Nagata, Kazuhiro
	NRID 1000060346145 1000060346145 researchmap permalink shimomura_i shimomura_i Scopus Author ID 7006715546 7006715546 ORCID 0000-0002-0851-9603 0000-0002-0851-9603 CreatorName Shimomura, Iichiro
Description	Shin J., Toyoda S., Okuno Y., et al. HSP47 levels determine the degree of body adiposity. Nature Communications 14, 7319 (2023); https://doi.org/10.1038/s41467-023-43080-x.
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.
Publisher	Nature Research
Source Title	Nature Communications
Volume (Issue)	14
Page	7319
Date of Issued	2023-11-11
Language	English
Handle URL	https://hdl.handle.net/11094/93378
eISSN	20411723
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1038/s41467-023-43080-x
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	Nature Communications. 2023, 14, p. 7319
DC.title	HSP47 levels determine the degree of body adiposity
DC.creator	Shin, Jihoon
	Toyoda, Shinichiro
	Okuno, Yosuke
	Hayashi, Reiko
	Nishitani, Shigeki
	Onodera, Toshiharu
	Sakamoto, Haruyo
	Ito, Shinya
	Kobayashi, Sachiko
	Nagao, Hirofumi
	Kita, Shunbun
	Otsuki, Michio
	Fukuhara, Atsunori
	Nagata, Kazuhiro
	Shimomura, Iichiro
DC.publisher	Nature Research
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2023-11-11
DC.identifier	https://doi.org/10.1038/s41467-023-43080-x
DC.description	Shin J., Toyoda S., Okuno Y., et al. HSP47 levels determine the degree of body adiposity. Nature Communications 14, 7319 (2023); https://doi.org/10.1038/s41467-023-43080-x.
DCTERMS.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.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	93378
citation_title	HSP47 levels determine the degree of body adiposity
citation_author	Shin, Jihoon
	Toyoda, Shinichiro
	Okuno, Yosuke
	Hayashi, Reiko
	Nishitani, Shigeki
	Onodera, Toshiharu
	Sakamoto, Haruyo
	Ito, Shinya
	Kobayashi, Sachiko
	Nagao, Hirofumi
	Kita, Shunbun
	Otsuki, Michio
	Fukuhara, Atsunori
	Nagata, Kazuhiro
	Shimomura, Iichiro
citation_publisher	Nature Research
citation_language	English
citation_date	2023-11-11
citation_journal_title	Nature Communications
citation_volume	14
citation_firstpage	7319
citation_doi	https://doi.org/10.1038/s41467-023-43080-x
citation_public_url	https://hdl.handle.net/11094/93378

HSP47 levels determine the degree of body adiposity

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