The Adipocyte Acquires a Fibroblast-Like Transcriptional Signature in Response to a High Fat Diet

被引:60
作者
Jones, Jessica E. C. [1 ,2 ]
Rabhi, Nabil [1 ]
Orofino, Joseph [1 ]
Gamini, Ramya [2 ]
Perissi, Valentina [1 ]
Vernochet, Cecile [2 ]
Farmer, Stephen R. [1 ]
机构
[1] Boston Univ, Sch Med, Dept Biochem, 72 East Concord St, Boston, MA USA
[2] Pfizer Inc, Internal Med Res Unit, Worldwide Res Dev & Med, 1 Portland St, Cambridge, MA 02139 USA
关键词
ADIPOSE-TISSUE FIBROSIS; EXTRACELLULAR-MATRIX; GENE-EXPRESSION; OBESITY; ACTIN; PROGENITORS; MODULATION; DYNAMICS; MURINE; MYOFIBROBLASTS;
D O I
10.1038/s41598-020-59284-w
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
Visceral white adipose tissue (vWAT) expands and undergoes extensive remodeling during diet-induced obesity. Much is known about the contribution of various stromal vascular cells to the remodeling process, but less is known of the changes that occur within the adipocyte as it becomes progressively dysfunctional. Here, we performed a transcriptome analysis of isolated vWAT adipocytes to assess global pathway changes occurring in response to a chronic high fat diet (HFD). The data demonstrate that the adipocyte responds to the HFD by adopting a fibroblast-like phenotype, characterized by enhanced expression of ECM, focal adhesion and cytoskeletal genes and suppression of many adipocyte programs most notably those associated with mitochondria. This study reveals that during obesity the adipocyte progressively becomes metabolically dysfunctional due to its acquisition of fibrogenic functions. We propose that mechano-responsive transcription factors such as MRTFA and SRF contribute to both upregulation of morphological genes as well as suppression of mitochondrial programs.
引用
收藏
页数:15
相关论文
共 79 条
[1]   Characterization of the adipocyte cellular lineage in vivo [J].
Berry, Ryan ;
Rodeheffer, Matthew S. .
NATURE CELL BIOLOGY, 2013, 15 (03) :302-308
[2]   Tenascin-C drives persistence of organ fibrosis [J].
Bhattacharyya, Swati ;
Wang, Wenxia ;
Morales-Nebreda, Luisa ;
Feng, Gang ;
Wu, Minghua ;
Zhou, Xiaodong ;
Lafyatis, Robert ;
Lee, Jungwha ;
Hinchcliff, Monique ;
Feghali-Bostwick, Carol ;
Lakota, Katja ;
Budinger, G. R. Scott ;
Raparia, Kirtee ;
Tamaki, Zenshiro ;
Varga, John .
NATURE COMMUNICATIONS, 2016, 7
[3]   Trimmomatic: a flexible trimmer for Illumina sequence data [J].
Bolger, Anthony M. ;
Lohse, Marc ;
Usadel, Bjoern .
BIOINFORMATICS, 2014, 30 (15) :2114-2120
[4]   Unconventional myosin Myo1c promotes membrane fusion in a regulated exocytic pathway [J].
Bose, A ;
Robida, S ;
Furcinitti, PS ;
Chawla, A ;
Fogarty, K ;
Corvera, S ;
Czech, MP .
MOLECULAR AND CELLULAR BIOLOGY, 2004, 24 (12) :5447-5458
[5]   Extracellular matrix, integrins, and growth factors as tailors of the stem cell niche [J].
Brizzi, Maria Felice ;
Tarone, Guido ;
Defilippi, Paola .
CURRENT OPINION IN CELL BIOLOGY, 2012, 24 (05) :645-651
[6]   MitoCarta2.0: an updated inventory of mammalian mitochondrial proteins [J].
Calvo, Sarah E. ;
Clauser, Karl R. ;
Mootha, Vamsi K. .
NUCLEIC ACIDS RESEARCH, 2016, 44 (D1) :D1251-D1257
[7]   Angiogenesis and Vascular Functions in Modulation of Obesity, Adipose Metabolism, and Insulin Sensitivity [J].
Cao, Yihai .
CELL METABOLISM, 2013, 18 (04) :478-489
[8]   Enrichr: interactive and collaborative HTML']HTML5 gene list enrichment analysis tool [J].
Chen, Edward Y. ;
Tan, Christopher M. ;
Kou, Yan ;
Duan, Qiaonan ;
Wang, Zichen ;
Meirelles, Gabriela Vaz ;
Clark, Neil R. ;
Ma'ayan, Avi .
BMC BIOINFORMATICS, 2013, 14
[9]  
Consortium T. G. O, 2000, NAT GENET, V25
[10]   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