Transcriptome analysis of ciliary-dependent MCH signaling in differentiating 3T3-L1 pre-adipocytes

Abstract An understanding of adipocyte responsiveness to G-protein-coupled receptor-(GPCR) derived signals must take into consideration the role of membrane microenvironments; that individual sub-populations of proteins may vary significantly across different regions of the cell, and that cell diffe...

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Autores principales:	Laurie B. Cook, Henry D. Ophardt, Rongkun Shen, Bryan H. Pratt, Lucas A. Galbier
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/39155f32a12d493d91ed7d75f3d18098
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spelling	oai:doaj.org-article:39155f32a12d493d91ed7d75f3d180982021-12-02T15:54:13ZTranscriptome analysis of ciliary-dependent MCH signaling in differentiating 3T3-L1 pre-adipocytes10.1038/s41598-021-84138-42045-2322https://doaj.org/article/39155f32a12d493d91ed7d75f3d180982021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84138-4https://doaj.org/toc/2045-2322Abstract An understanding of adipocyte responsiveness to G-protein-coupled receptor-(GPCR) derived signals must take into consideration the role of membrane microenvironments; that individual sub-populations of proteins may vary significantly across different regions of the cell, and that cell differentiation alters those microenvironments. 3T3-L1 pre-adipocytes undergo a dramatic phenotypic transformation during differentiation into adipocytes, requiring the development of a transient primary cilium. We demonstrate that melanin-concentrating hormone (MCH) receptor 1, a GPCR that stimulates appetite, translocates to the transient primary cilium during early 3T3-L1 cell adipogenesis. Furthermore, we used RNA-Seq to investigate whether MCH signaling is influenced by its receptor localization and whether MCH can influence the transcriptome of early adipocyte development. We found that MCH signaling is sensitive to receptor localization to cilia, and this alters the adipogenic transcriptional program. Also, novel MCH signaling pathways in 3T3-L1 cells are identified, including those for circadian rhythm, the inflammatory response, and ciliary biogenesis. The presence of active MCH-signaling pathways in pre-adipocytes and the discovery that these pathways intersect with the early adipogenic program, among other newly-identified signaling pathways, suggests that the use of MCH receptor 1 antagonists for clinical interventions may have unintended consequences on adipose tissue development.Laurie B. CookHenry D. OphardtRongkun ShenBryan H. PrattLucas A. GalbierNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Laurie B. Cook Henry D. Ophardt Rongkun Shen Bryan H. Pratt Lucas A. Galbier Transcriptome analysis of ciliary-dependent MCH signaling in differentiating 3T3-L1 pre-adipocytes
description	Abstract An understanding of adipocyte responsiveness to G-protein-coupled receptor-(GPCR) derived signals must take into consideration the role of membrane microenvironments; that individual sub-populations of proteins may vary significantly across different regions of the cell, and that cell differentiation alters those microenvironments. 3T3-L1 pre-adipocytes undergo a dramatic phenotypic transformation during differentiation into adipocytes, requiring the development of a transient primary cilium. We demonstrate that melanin-concentrating hormone (MCH) receptor 1, a GPCR that stimulates appetite, translocates to the transient primary cilium during early 3T3-L1 cell adipogenesis. Furthermore, we used RNA-Seq to investigate whether MCH signaling is influenced by its receptor localization and whether MCH can influence the transcriptome of early adipocyte development. We found that MCH signaling is sensitive to receptor localization to cilia, and this alters the adipogenic transcriptional program. Also, novel MCH signaling pathways in 3T3-L1 cells are identified, including those for circadian rhythm, the inflammatory response, and ciliary biogenesis. The presence of active MCH-signaling pathways in pre-adipocytes and the discovery that these pathways intersect with the early adipogenic program, among other newly-identified signaling pathways, suggests that the use of MCH receptor 1 antagonists for clinical interventions may have unintended consequences on adipose tissue development.
format	article
author	Laurie B. Cook Henry D. Ophardt Rongkun Shen Bryan H. Pratt Lucas A. Galbier
author_facet	Laurie B. Cook Henry D. Ophardt Rongkun Shen Bryan H. Pratt Lucas A. Galbier
author_sort	Laurie B. Cook
title	Transcriptome analysis of ciliary-dependent MCH signaling in differentiating 3T3-L1 pre-adipocytes
title_short	Transcriptome analysis of ciliary-dependent MCH signaling in differentiating 3T3-L1 pre-adipocytes
title_full	Transcriptome analysis of ciliary-dependent MCH signaling in differentiating 3T3-L1 pre-adipocytes
title_fullStr	Transcriptome analysis of ciliary-dependent MCH signaling in differentiating 3T3-L1 pre-adipocytes
title_full_unstemmed	Transcriptome analysis of ciliary-dependent MCH signaling in differentiating 3T3-L1 pre-adipocytes
title_sort	transcriptome analysis of ciliary-dependent mch signaling in differentiating 3t3-l1 pre-adipocytes
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/39155f32a12d493d91ed7d75f3d18098
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Transcriptome analysis of ciliary-dependent MCH signaling in differentiating 3T3-L1 pre-adipocytes

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