Direct conversion of human fibroblasts to brown adipocytes by small chemical compounds

Abstract Brown adipocytes play an important role in human energy metabolism and prevention of obesity and diabetes. Induced pluripotent stem cells (iPSCs) represent a promising source for brown adipocytes; however, exogenous gene induction is generally required for iPSCs generation, which might caus...

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Autores principales:	Yukimasa Takeda, Yoshinori Harada, Toshikazu Yoshikawa, Ping Dai
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5912ca5dc598460a88e8292ed8005d9a
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spelling	oai:doaj.org-article:5912ca5dc598460a88e8292ed8005d9a2021-12-02T12:32:11ZDirect conversion of human fibroblasts to brown adipocytes by small chemical compounds10.1038/s41598-017-04665-x2045-2322https://doaj.org/article/5912ca5dc598460a88e8292ed8005d9a2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04665-xhttps://doaj.org/toc/2045-2322Abstract Brown adipocytes play an important role in human energy metabolism and prevention of obesity and diabetes. Induced pluripotent stem cells (iPSCs) represent a promising source for brown adipocytes; however, exogenous gene induction is generally required for iPSCs generation, which might cause undesired effects particularly in long-term treatment after transplantation. We have previously reported a cocktail of six small chemical compounds that enables a conversion of human fibroblasts into chemical compound-induced neuronal cells (CiNCs). Here, we report that modified combinations of the chemical compounds and rosiglitazone, a PPARγ agonist, afforded direct conversion of human fibroblasts into brown adipocytes. The chemical compound-induced brown adipocytes (ciBAs) exhibit induction of human brown adipocyte-specific genes such as Ucp1, Ckmt1, Cited1 and other adipocyte-specific genes such as Fabp4, AdipoQ, and Pparγ. Treatment with either isoproterenol or Forskolin further induced the expression of Ucp1, suggesting that β adrenergic receptor signalling in ciBAs could be functional for induction of thermogenic genes. Moreover, oxygen consumption rates were elevated in ciBAs along with increase of cellular mitochondria. Our findings might provide an easily accessible approach for generating human brown adipocytes from fibroblasts and offer therapeutic potential for the management of obesity, diabetes, and related metabolic disorders.Yukimasa TakedaYoshinori HaradaToshikazu YoshikawaPing DaiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yukimasa Takeda Yoshinori Harada Toshikazu Yoshikawa Ping Dai Direct conversion of human fibroblasts to brown adipocytes by small chemical compounds
description	Abstract Brown adipocytes play an important role in human energy metabolism and prevention of obesity and diabetes. Induced pluripotent stem cells (iPSCs) represent a promising source for brown adipocytes; however, exogenous gene induction is generally required for iPSCs generation, which might cause undesired effects particularly in long-term treatment after transplantation. We have previously reported a cocktail of six small chemical compounds that enables a conversion of human fibroblasts into chemical compound-induced neuronal cells (CiNCs). Here, we report that modified combinations of the chemical compounds and rosiglitazone, a PPARγ agonist, afforded direct conversion of human fibroblasts into brown adipocytes. The chemical compound-induced brown adipocytes (ciBAs) exhibit induction of human brown adipocyte-specific genes such as Ucp1, Ckmt1, Cited1 and other adipocyte-specific genes such as Fabp4, AdipoQ, and Pparγ. Treatment with either isoproterenol or Forskolin further induced the expression of Ucp1, suggesting that β adrenergic receptor signalling in ciBAs could be functional for induction of thermogenic genes. Moreover, oxygen consumption rates were elevated in ciBAs along with increase of cellular mitochondria. Our findings might provide an easily accessible approach for generating human brown adipocytes from fibroblasts and offer therapeutic potential for the management of obesity, diabetes, and related metabolic disorders.
format	article
author	Yukimasa Takeda Yoshinori Harada Toshikazu Yoshikawa Ping Dai
author_facet	Yukimasa Takeda Yoshinori Harada Toshikazu Yoshikawa Ping Dai
author_sort	Yukimasa Takeda
title	Direct conversion of human fibroblasts to brown adipocytes by small chemical compounds
title_short	Direct conversion of human fibroblasts to brown adipocytes by small chemical compounds
title_full	Direct conversion of human fibroblasts to brown adipocytes by small chemical compounds
title_fullStr	Direct conversion of human fibroblasts to brown adipocytes by small chemical compounds
title_full_unstemmed	Direct conversion of human fibroblasts to brown adipocytes by small chemical compounds
title_sort	direct conversion of human fibroblasts to brown adipocytes by small chemical compounds
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/5912ca5dc598460a88e8292ed8005d9a
work_keys_str_mv	AT yukimasatakeda directconversionofhumanfibroblaststobrownadipocytesbysmallchemicalcompounds AT yoshinoriharada directconversionofhumanfibroblaststobrownadipocytesbysmallchemicalcompounds AT toshikazuyoshikawa directconversionofhumanfibroblaststobrownadipocytesbysmallchemicalcompounds AT pingdai directconversionofhumanfibroblaststobrownadipocytesbysmallchemicalcompounds
_version_	1718394158145601536

Direct conversion of human fibroblasts to brown adipocytes by small chemical compounds

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