Cargando…

Direct conversion of human myoblasts into brown-like adipocytes by engineered superactive PPARγ

OBJECTIVE: To determine whether super-activation of PPARγ can reprogram human myoblasts into brownlike adipocytes and to establish a new cell model for browning research. METHODS: To enhance the PPARγ signaling, we fused M3, the transactivation domain of MyoD, to PPARγ. PPARγ and M3-PPARγ-lentiviral...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhu, Yanbei, Yang, Rongze, McLenithan, John, Yu, Daozhan, Wang, Hong, Wang, Yaping, Singh, Devinder, Olson, John, Sztalryd, Carole, Zhu, Dalong, Gong, Da-Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4413469/
https://www.ncbi.nlm.nih.gov/pubmed/25919922
http://dx.doi.org/10.1002/oby.21062
_version_ 1782368784093282304
author Zhu, Yanbei
Yang, Rongze
McLenithan, John
Yu, Daozhan
Wang, Hong
Wang, Yaping
Singh, Devinder
Olson, John
Sztalryd, Carole
Zhu, Dalong
Gong, Da-Wei
author_facet Zhu, Yanbei
Yang, Rongze
McLenithan, John
Yu, Daozhan
Wang, Hong
Wang, Yaping
Singh, Devinder
Olson, John
Sztalryd, Carole
Zhu, Dalong
Gong, Da-Wei
author_sort Zhu, Yanbei
collection PubMed
description OBJECTIVE: To determine whether super-activation of PPARγ can reprogram human myoblasts into brownlike adipocytes and to establish a new cell model for browning research. METHODS: To enhance the PPARγ signaling, we fused M3, the transactivation domain of MyoD, to PPARγ. PPARγ and M3-PPARγ-lentiviral vectors were used to convert human myoblasts into adipocytes. Brown adipocyte markers of the reprogrammed adipocytes were assessed by qPCR and protein analyses. White adipocytes differentiated from subcutaneous stromal vascular cells and perithyroid brown fat tissues were used as references. RESULTS: In transient transfection, M3-PPARγ has stronger constitutive activity than PPARγ reporter assay. Although both the transduction of PPARγ and M3-PPARγ induced adipogenesis in myoblasts, M3-PPARγ, compared to PPARγ, drastically induced the brown adipocyte markers of UCP1, CIDEA and PRDM16 by 1,050, 2.4, and 5.0 fold, respectively and increased mitochondria contents by 4 fold. The gene expression levels of the browning makers in PPARγ-reprogrammed adipocytes are comparable to those of in vitro differentiated white adipocytes. CONCLUSIONS: We have found that super-activation of PPARγ can effectively convert human myoblasts into brown-like adipocytes and can be a new approach to derive brown-like adipocytes.
format Online
Article
Text
id pubmed-4413469
institution National Center for Biotechnology Information
language English
publishDate 2015
record_format MEDLINE/PubMed
spelling pubmed-44134692016-05-01 Direct conversion of human myoblasts into brown-like adipocytes by engineered superactive PPARγ Zhu, Yanbei Yang, Rongze McLenithan, John Yu, Daozhan Wang, Hong Wang, Yaping Singh, Devinder Olson, John Sztalryd, Carole Zhu, Dalong Gong, Da-Wei Obesity (Silver Spring) Article OBJECTIVE: To determine whether super-activation of PPARγ can reprogram human myoblasts into brownlike adipocytes and to establish a new cell model for browning research. METHODS: To enhance the PPARγ signaling, we fused M3, the transactivation domain of MyoD, to PPARγ. PPARγ and M3-PPARγ-lentiviral vectors were used to convert human myoblasts into adipocytes. Brown adipocyte markers of the reprogrammed adipocytes were assessed by qPCR and protein analyses. White adipocytes differentiated from subcutaneous stromal vascular cells and perithyroid brown fat tissues were used as references. RESULTS: In transient transfection, M3-PPARγ has stronger constitutive activity than PPARγ reporter assay. Although both the transduction of PPARγ and M3-PPARγ induced adipogenesis in myoblasts, M3-PPARγ, compared to PPARγ, drastically induced the brown adipocyte markers of UCP1, CIDEA and PRDM16 by 1,050, 2.4, and 5.0 fold, respectively and increased mitochondria contents by 4 fold. The gene expression levels of the browning makers in PPARγ-reprogrammed adipocytes are comparable to those of in vitro differentiated white adipocytes. CONCLUSIONS: We have found that super-activation of PPARγ can effectively convert human myoblasts into brown-like adipocytes and can be a new approach to derive brown-like adipocytes. 2015-05 /pmc/articles/PMC4413469/ /pubmed/25919922 http://dx.doi.org/10.1002/oby.21062 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Zhu, Yanbei
Yang, Rongze
McLenithan, John
Yu, Daozhan
Wang, Hong
Wang, Yaping
Singh, Devinder
Olson, John
Sztalryd, Carole
Zhu, Dalong
Gong, Da-Wei
Direct conversion of human myoblasts into brown-like adipocytes by engineered superactive PPARγ
title Direct conversion of human myoblasts into brown-like adipocytes by engineered superactive PPARγ
title_full Direct conversion of human myoblasts into brown-like adipocytes by engineered superactive PPARγ
title_fullStr Direct conversion of human myoblasts into brown-like adipocytes by engineered superactive PPARγ
title_full_unstemmed Direct conversion of human myoblasts into brown-like adipocytes by engineered superactive PPARγ
title_short Direct conversion of human myoblasts into brown-like adipocytes by engineered superactive PPARγ
title_sort direct conversion of human myoblasts into brown-like adipocytes by engineered superactive pparγ
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4413469/
https://www.ncbi.nlm.nih.gov/pubmed/25919922
http://dx.doi.org/10.1002/oby.21062
work_keys_str_mv AT zhuyanbei directconversionofhumanmyoblastsintobrownlikeadipocytesbyengineeredsuperactivepparg
AT yangrongze directconversionofhumanmyoblastsintobrownlikeadipocytesbyengineeredsuperactivepparg
AT mclenithanjohn directconversionofhumanmyoblastsintobrownlikeadipocytesbyengineeredsuperactivepparg
AT yudaozhan directconversionofhumanmyoblastsintobrownlikeadipocytesbyengineeredsuperactivepparg
AT wanghong directconversionofhumanmyoblastsintobrownlikeadipocytesbyengineeredsuperactivepparg
AT wangyaping directconversionofhumanmyoblastsintobrownlikeadipocytesbyengineeredsuperactivepparg
AT singhdevinder directconversionofhumanmyoblastsintobrownlikeadipocytesbyengineeredsuperactivepparg
AT olsonjohn directconversionofhumanmyoblastsintobrownlikeadipocytesbyengineeredsuperactivepparg
AT sztalrydcarole directconversionofhumanmyoblastsintobrownlikeadipocytesbyengineeredsuperactivepparg
AT zhudalong directconversionofhumanmyoblastsintobrownlikeadipocytesbyengineeredsuperactivepparg
AT gongdawei directconversionofhumanmyoblastsintobrownlikeadipocytesbyengineeredsuperactivepparg