Prolyl Isomerase Pin1 Suppresses Thermogenic Programs in Adipocytes by Promoting Degradation of Transcriptional Co-activator PRDM16

Yusuke Nakatsu; Yasuka Matsunaga; Takeshi Yamamotoya; Koji Ueda; Masa ki Inoue; Yu Mizuno; Mikako Nakanishi; Tomomi Sano; Yosuke Yamawaki; Akifumi Kushiyama; Hideyuki Sakoda; Midori Fujishiro; Akihide Ryo; Hiraku Ono; Tohru Minamino; Shin Ichiro Takahashi; Haruya Ohno; Masayasu Yoneda; Kei Takahashi; Hisamitsu Ishihara; Hideki Katagiri; Fusanori Nishimura; Takashi Kanematsu; Tetsuya Yamada; Tomoichiro Asano

doi:10.1016/j.celrep.2019.02.066

Prolyl Isomerase Pin1 Suppresses Thermogenic Programs in Adipocytes by Promoting Degradation of Transcriptional Co-activator PRDM16

Yusuke Nakatsu, Yasuka Matsunaga, Takeshi Yamamotoya, Koji Ueda, Masa ki Inoue, Yu Mizuno, Mikako Nakanishi, Tomomi Sano, Yosuke Yamawaki, Akifumi Kushiyama, Hideyuki Sakoda, Midori Fujishiro, Akihide Ryo, Hiraku Ono, Tohru Minamino, Shin Ichiro Takahashi, Haruya Ohno, Masayasu Yoneda, Kei Takahashi, Hisamitsu IshiharaHideki Katagiri, Fusanori Nishimura, Takashi Kanematsu, Tetsuya Yamada, Tomoichiro Asano

Research output: Contribution to journal › Article › peer-review

19 Citations (Scopus)

Abstract

Non-shivering thermogenesis in adipocytes provides defense against low temperatures and obesity development, but the underlying regulatory mechanism remains to be fully clarified. Based on both markedly increased Pin1 expression in states of excess nutrition and resistance to obesity development in Pin1 null mice, we speculated that adipocyte Pin1 may play a role in thermogenic programs. Adipose-specific Pin1 knockout (adPin1 KO) mice showed enhanced transcription of thermogenic genes and tolerance to hypothermia when exposed to cold. In addition, adPin1 KO mice were resistant to high-fat diet-induced obesity and glucose intolerance. A series of experiments revealed that Pin1 binds to PRDM16 and thereby promotes its degradation through the ubiquitin-proteasome system. Consistent with these results, Pin1 deletion in differentiated adipocytes showed enhancement of thermogenic programs in response to the β3 agonist CL316243 through the upregulation of PRDM16 proteins. These observations indicate that Pin1 is a negative regulator of non-shivering thermogenesis.

Original language	English
Pages (from-to)	3221-3230.e3
Journal	Cell Reports
Volume	26
Issue number	12
DOIs	https://doi.org/10.1016/j.celrep.2019.02.066
Publication status	Published - 19 Mar 2019
Externally published	Yes

Keywords

obesity
Pin1
PRDM16
thermogenesis
UCP-1

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.celrep.2019.02.066

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Nakatsu, Y., Matsunaga, Y., Yamamotoya, T., Ueda, K., Inoue, M. K., Mizuno, Y., Nakanishi, M., Sano, T., Yamawaki, Y., Kushiyama, A., Sakoda, H., Fujishiro, M., Ryo, A., Ono, H., Minamino, T., Takahashi, S. I., Ohno, H., Yoneda, M., Takahashi, K., ... Asano, T. (2019). Prolyl Isomerase Pin1 Suppresses Thermogenic Programs in Adipocytes by Promoting Degradation of Transcriptional Co-activator PRDM16. Cell Reports, 26(12), 3221-3230.e3. https://doi.org/10.1016/j.celrep.2019.02.066

@article{d9e114f2c3db4d0282755d2e7a8d5fa0,

title = "Prolyl Isomerase Pin1 Suppresses Thermogenic Programs in Adipocytes by Promoting Degradation of Transcriptional Co-activator PRDM16",

abstract = "Non-shivering thermogenesis in adipocytes provides defense against low temperatures and obesity development, but the underlying regulatory mechanism remains to be fully clarified. Based on both markedly increased Pin1 expression in states of excess nutrition and resistance to obesity development in Pin1 null mice, we speculated that adipocyte Pin1 may play a role in thermogenic programs. Adipose-specific Pin1 knockout (adPin1 KO) mice showed enhanced transcription of thermogenic genes and tolerance to hypothermia when exposed to cold. In addition, adPin1 KO mice were resistant to high-fat diet-induced obesity and glucose intolerance. A series of experiments revealed that Pin1 binds to PRDM16 and thereby promotes its degradation through the ubiquitin-proteasome system. Consistent with these results, Pin1 deletion in differentiated adipocytes showed enhancement of thermogenic programs in response to the β3 agonist CL316243 through the upregulation of PRDM16 proteins. These observations indicate that Pin1 is a negative regulator of non-shivering thermogenesis.",

keywords = "obesity, Pin1, PRDM16, thermogenesis, UCP-1",

author = "Yusuke Nakatsu and Yasuka Matsunaga and Takeshi Yamamotoya and Koji Ueda and Inoue, {Masa ki} and Yu Mizuno and Mikako Nakanishi and Tomomi Sano and Yosuke Yamawaki and Akifumi Kushiyama and Hideyuki Sakoda and Midori Fujishiro and Akihide Ryo and Hiraku Ono and Tohru Minamino and Takahashi, {Shin Ichiro} and Haruya Ohno and Masayasu Yoneda and Kei Takahashi and Hisamitsu Ishihara and Hideki Katagiri and Fusanori Nishimura and Takashi Kanematsu and Tetsuya Yamada and Tomoichiro Asano",

note = "Publisher Copyright: {\textcopyright} 2019 The Authors",

year = "2019",

month = mar,

day = "19",

doi = "10.1016/j.celrep.2019.02.066",

language = "English",

volume = "26",

pages = "3221--3230.e3",

journal = "Cell Reports",

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Nakatsu, Y, Matsunaga, Y, Yamamotoya, T, Ueda, K, Inoue, MK, Mizuno, Y, Nakanishi, M, Sano, T, Yamawaki, Y, Kushiyama, A, Sakoda, H, Fujishiro, M, Ryo, A, Ono, H, Minamino, T, Takahashi, SI, Ohno, H, Yoneda, M, Takahashi, K, Ishihara, H, Katagiri, H, Nishimura, F, Kanematsu, T, Yamada, T & Asano, T 2019, 'Prolyl Isomerase Pin1 Suppresses Thermogenic Programs in Adipocytes by Promoting Degradation of Transcriptional Co-activator PRDM16', Cell Reports, vol. 26, no. 12, pp. 3221-3230.e3. https://doi.org/10.1016/j.celrep.2019.02.066

TY - JOUR

T1 - Prolyl Isomerase Pin1 Suppresses Thermogenic Programs in Adipocytes by Promoting Degradation of Transcriptional Co-activator PRDM16

AU - Nakatsu, Yusuke

AU - Matsunaga, Yasuka

AU - Yamamotoya, Takeshi

AU - Ueda, Koji

AU - Inoue, Masa ki

AU - Mizuno, Yu

AU - Nakanishi, Mikako

AU - Sano, Tomomi

AU - Yamawaki, Yosuke

AU - Kushiyama, Akifumi

AU - Sakoda, Hideyuki

AU - Fujishiro, Midori

AU - Ryo, Akihide

AU - Ono, Hiraku

AU - Minamino, Tohru

AU - Takahashi, Shin Ichiro

AU - Ohno, Haruya

AU - Yoneda, Masayasu

AU - Takahashi, Kei

AU - Ishihara, Hisamitsu

AU - Katagiri, Hideki

AU - Nishimura, Fusanori

AU - Kanematsu, Takashi

AU - Yamada, Tetsuya

AU - Asano, Tomoichiro

PY - 2019/3/19

Y1 - 2019/3/19

N2 - Non-shivering thermogenesis in adipocytes provides defense against low temperatures and obesity development, but the underlying regulatory mechanism remains to be fully clarified. Based on both markedly increased Pin1 expression in states of excess nutrition and resistance to obesity development in Pin1 null mice, we speculated that adipocyte Pin1 may play a role in thermogenic programs. Adipose-specific Pin1 knockout (adPin1 KO) mice showed enhanced transcription of thermogenic genes and tolerance to hypothermia when exposed to cold. In addition, adPin1 KO mice were resistant to high-fat diet-induced obesity and glucose intolerance. A series of experiments revealed that Pin1 binds to PRDM16 and thereby promotes its degradation through the ubiquitin-proteasome system. Consistent with these results, Pin1 deletion in differentiated adipocytes showed enhancement of thermogenic programs in response to the β3 agonist CL316243 through the upregulation of PRDM16 proteins. These observations indicate that Pin1 is a negative regulator of non-shivering thermogenesis.

AB - Non-shivering thermogenesis in adipocytes provides defense against low temperatures and obesity development, but the underlying regulatory mechanism remains to be fully clarified. Based on both markedly increased Pin1 expression in states of excess nutrition and resistance to obesity development in Pin1 null mice, we speculated that adipocyte Pin1 may play a role in thermogenic programs. Adipose-specific Pin1 knockout (adPin1 KO) mice showed enhanced transcription of thermogenic genes and tolerance to hypothermia when exposed to cold. In addition, adPin1 KO mice were resistant to high-fat diet-induced obesity and glucose intolerance. A series of experiments revealed that Pin1 binds to PRDM16 and thereby promotes its degradation through the ubiquitin-proteasome system. Consistent with these results, Pin1 deletion in differentiated adipocytes showed enhancement of thermogenic programs in response to the β3 agonist CL316243 through the upregulation of PRDM16 proteins. These observations indicate that Pin1 is a negative regulator of non-shivering thermogenesis.

KW - obesity

KW - Pin1

KW - PRDM16

KW - thermogenesis

KW - UCP-1

UR - http://www.scopus.com/inward/record.url?scp=85062807754&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2019.02.066

DO - 10.1016/j.celrep.2019.02.066

M3 - Article

C2 - 30893596

AN - SCOPUS:85062807754

SN - 2211-1247

VL - 26

SP - 3221-3230.e3

JO - Cell Reports

JF - Cell Reports

IS - 12

ER -

Prolyl Isomerase Pin1 Suppresses Thermogenic Programs in Adipocytes by Promoting Degradation of Transcriptional Co-activator PRDM16

Abstract

Keywords

UN SDGs

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