Zfp238 Regulates the Thermogenic Program in Cooperation with Foxo1

被引：13

作者：

Kita, Motoko ^{[1
]}

Nakae, Jun ^{[1
,2
]}

Kawano, Yoshinaga ^{[1
]}

Asahara, Hiroshi ^{[3
]}

Takemori, Hiroshi ^{[4
]}

Okado, Haruo ^{[5
]}

Itoh, Hiroshi ^{[1
]}

机构：

[1] Keio Univ, Div Endocrinol Metab & Nephrol, Navigat Med Kidney & Metab, Dept Internal Med,Sch Med, Tokyo 1608582, Japan

[2] Int Univ Hlth & Welf, Sch Med, Dept Physiol, Narita 2868686, Japan

[3] Tokyo Med & Dent Univ, Dept Syst BioMed, Tokyo 1138519, Japan

[4] Gifu Univ, Dept Chem & Biomol Sci, Fac Engn, Gifu 5011193, Japan

[5] Tokyo Metropolitan Inst Med Sci, Dept Brain Dev & Neural Regenerat, Setagaya Ku, Tokyo 1560057, Japan

来源：

ISCIENCE | 2019年 / 12卷

关键词：

BROWN ADIPOSE-TISSUE; TRANSCRIPTION FACTOR FOXO1; HIGH-FAT DIET; INSULIN SENSITIVITY; ADIPOCYTE DIFFERENTIATION; ENERGY-BALANCE; UCP1; GENE; PHOSPHORYLATION; MACROPHAGES; REPRESSOR;

D O I：

10.1016/j.isci.2019.01.005

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Obesity has become an explicit public health concern because of its relevance to metabolic syndrome. Evidence points to the significance of beige adipocytes in regulating energy expenditure. Here, using yeast two-hybrid screening, we show that Zfp238 is a Foxo1 co-repressor and that adipose-tissue-specific ablation of Zfp238 (Adipo-Zfp238KO) in mice leads to obesity, decreased energy expenditure, and insulin resistance under normal chow diet. Adipo-Zfp238KO inhibits induction of Ucp1 expression in subcutaneous adipose tissue upon cold exposure or CL316243, but not in brown adipose tissue. Furthermore, knockdown of Zfp238 in 3T3-L1 cells decreases Ucp1 expression in response to cool incubation or forskolin significantly compared with control cells. In contrast, overexpression of Zfp238 in 3T3-L1 cells significantly increases Ucp1 expression in response to forskolin. Finally, double knockdown of both Zfp238 and Foxo1 normalizes Ucp1 induction. These data suggest that Zfp238 in adipose tissue regulates the thermogenic program in cooperation with Foxo1.

引用

页码：87 / +

页数：32

共 52 条

[1] RP58 associates with condensed chromatin and mediates a sequence-specific transcriptional repression [J].

Aoki, K ;

Meng, GY ;

Suzuki, K ;

Takashi, T ;

Kameoka, Y ;

Nakahara, K ;

Ishida, R ;

Kasai, M .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (41) :26698-26704

[2] Brown adipose tissue: Function and physiological significance [J].

Cannon, B ;

Nedergaard, J .

PHYSIOLOGICAL REVIEWS, 2004, 84 (01) :277-359

[3] Brown adipose tissue - More than an effector of thermogenesis? [J].

Cannon, B ;

Houstek, J ;

Nedergaard, J .

MOLECULAR MECHANISMS OF FEVER, 1998, 856 :171-187

[4] The Protein Kinase IKKε Regulates Energy Balance in Obese Mice [J].

Chiang, Shian-Huey ;

Bazuine, Merlijn ;

Lumeng, Carey N. ;

Geletka, Lynn M. ;

Mowers, Jonathan ;

White, Nicole M. ;

Ma, Jing-Tyan ;

Zhou, Jie ;

Qi, Nathan ;

Westcott, Dan ;

Delproposto, Jennifer B. ;

Blackwell, Timothy S. ;

Yull, Fiona E. ;

Saltiel, Alan R. .

CELL, 2009, 138 (05) :961-975

[5] Protein arginine methyltransferase 1 regulates hepatic glucose production in a FoxO1-dependent manner [J].

Choi, Dahee ;

Oh, Kyoung-Jin ;

Han, Hye-Sook ;

Yoon, Young-Sil ;

Jung, Chang-Yun ;

Kim, Seong-Tae ;

Koo, Seung-Hoi .

HEPATOLOGY, 2012, 56 (04) :1546-1556

[6] Positive and negative control of Ucp1 gene transcription and the role of β-adrenergic signaling networks [J].

Collins, S. ;

Yehuda-Shnaidman, E. ;

Wang, H. .

INTERNATIONAL JOURNAL OF OBESITY, 2010, 34 :S28-S33

[7] Identification and Importance of Brown Adipose Tissue in Adult Humans. [J].

Cypess, Aaron M. ;

Lehman, Sanaz ;

Williams, Gethin ;

Tal, Ilan ;

Rodman, Dean ;

Goldfine, Allison B. ;

Kuo, Frank C. ;

Palmer, Edwin L. ;

Tseng, Yu-Hua ;

Doria, Alessandro ;

Kolodny, Gerald M. ;

Kahn, C. Ronald .

NEW ENGLAND JOURNAL OF MEDICINE, 2009, 360 (15) :1509-1517

[8] Cold-Inducible Zfp516 Activates UCP1 Transcription to Promote Browning of White Fat and Development of Brown Fat [J].

Dempersmier, Jon ;

Sambeat, Audrey ;

Gulyaeva, Olga ;

Paul, Sarah M. ;

Hudak, Carolyn S. S. ;

Raposo, Helena F. ;

Kwan, Hiu-Yee ;

Kang, Chulho ;

Wong, Roger H. F. ;

Sul, Hei Sook .

MOLECULAR CELL, 2015, 57 (02) :235-246

[9] Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19.2 million participants [J].

Di Cesare, Mariachiara ;

Bentham, James ;

Stevens, Gretchen A. ;

Zhou, Bin ;

Danaei, Goodarz ;

Lu, Yuan ;

Bixby, Honor ;

Cowan, Melanie J. ;

Riley, Leanne M. ;

Hajifathalian, Kaveh ;

Fortunato, Lea ;

Taddei, Cristina ;

Bennett, James E. ;

Ikeda, Nayu ;

Khang, Young-Ho ;

Kyobutungi, Catherine ;

Laxmaiah, Avula ;

Li, Yanping ;

Lin, Hsien-Ho ;

Miranda, J. Jaime ;

Mostafa, Aya ;

Turley, Maria L. ;

Paciorek, Christopher J. ;

Gunter, Marc ;

Ezzati, Majid ;

Abdeen, Ziad A. ;

Hamid, Zargar Abdul ;

Abu-Rmeileh, Niveen M. ;

Acosta-Cazares, Benjamin ;

Adams, Robert ;

Aekplakorn, Wichai ;

Aguilar-Salinas, Carlos A. ;

Ahmadvand, Alireza ;

Ahrens, Wolfgang ;

Ali, Mohamed M. ;

Alkerwi, Ala'a ;

Alvarez-Pedrerol, Mar ;

Aly, Eman ;

Amouyel, Philippe ;

Amuzu, Antoinette ;

Andersen, Lars Bo ;

Anderssen, Sigmund A. ;

Andrade, Dolores S. ;

Anjana, Ranjit Mohan ;

Aounallah-Skhiri, Hajer ;

Ariansen, Inger ;

Aris, Tahir ;

Arlappa, Nimmathota ;

Arveiler, Dominique ;

Assah, Felix K. .

LANCET, 2016, 387 (10026) :1377-1396

[10] Transcriptional Control of Adipose Lipid Handling by IRF4 [J].

Eguchi, Jun ;

Wang, Xun ;

Yu, Songtao ;

Kershaw, Erin E. ;

Chiu, Patricia C. ;

Dushay, Joanne ;

Estall, Jennifer L. ;

Klein, Ulf ;

Maratos-Flier, Eleftheria ;

Rosen, Evan D. .

CELL METABOLISM, 2011, 13 (03) :249-259

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