Cargando…

CIDEA Transcriptionally Regulates UCP1 for Britening and Thermogenesis in Human Fat Cells

Our study identifies a transcriptional role of cell death-inducing DNA fragmentation factor-like effector A (CIDEA), a lipid-droplet-associated protein, whereby it regulates human adipocyte britening/beiging with consequences for the regulation of energy expenditure. The comprehensive transcriptome...

Descripción completa

Detalles Bibliográficos
Autores principales: Jash, Sukanta, Banerjee, Sayani, Lee, Mi-Jeong, Farmer, Stephen R., Puri, Vishwajeet
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6817690/
https://www.ncbi.nlm.nih.gov/pubmed/31563853
http://dx.doi.org/10.1016/j.isci.2019.09.011
_version_ 1783463476624097280
author Jash, Sukanta
Banerjee, Sayani
Lee, Mi-Jeong
Farmer, Stephen R.
Puri, Vishwajeet
author_facet Jash, Sukanta
Banerjee, Sayani
Lee, Mi-Jeong
Farmer, Stephen R.
Puri, Vishwajeet
author_sort Jash, Sukanta
collection PubMed
description Our study identifies a transcriptional role of cell death-inducing DNA fragmentation factor-like effector A (CIDEA), a lipid-droplet-associated protein, whereby it regulates human adipocyte britening/beiging with consequences for the regulation of energy expenditure. The comprehensive transcriptome analysis revealed CIDEA's control over thermogenic function in brite/beige human adipocytes. In the absence of CIDEA, achieved by the modified dual-RNA-based CRISPR-Cas9n(D10A) system, adipocytes lost their britening capability, which was recovered upon CIDEA re-expression. Uncoupling protein 1 (UCP1), the most upregulated gene in brite human adipocytes, was suppressed in CIDEA knockout (KO) primary human adipocytes. Mechanistically, during induced britening, CIDEA shuttled from lipid droplets to the nucleus via an unusual nuclear bipartite signal in a concentration-dependent manner. In the nucleus, it specifically inhibited LXRα repression of UCP1 enhancer activity and strengthened PPARγ binding to UCP1 enhancer, hence driving UCP1 transcription. Overall, our study defines the role of CIDEA in increasing thermogenesis in human adipocytes.
format Online
Article
Text
id pubmed-6817690
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Elsevier
record_format MEDLINE/PubMed
spelling pubmed-68176902019-10-31 CIDEA Transcriptionally Regulates UCP1 for Britening and Thermogenesis in Human Fat Cells Jash, Sukanta Banerjee, Sayani Lee, Mi-Jeong Farmer, Stephen R. Puri, Vishwajeet iScience Article Our study identifies a transcriptional role of cell death-inducing DNA fragmentation factor-like effector A (CIDEA), a lipid-droplet-associated protein, whereby it regulates human adipocyte britening/beiging with consequences for the regulation of energy expenditure. The comprehensive transcriptome analysis revealed CIDEA's control over thermogenic function in brite/beige human adipocytes. In the absence of CIDEA, achieved by the modified dual-RNA-based CRISPR-Cas9n(D10A) system, adipocytes lost their britening capability, which was recovered upon CIDEA re-expression. Uncoupling protein 1 (UCP1), the most upregulated gene in brite human adipocytes, was suppressed in CIDEA knockout (KO) primary human adipocytes. Mechanistically, during induced britening, CIDEA shuttled from lipid droplets to the nucleus via an unusual nuclear bipartite signal in a concentration-dependent manner. In the nucleus, it specifically inhibited LXRα repression of UCP1 enhancer activity and strengthened PPARγ binding to UCP1 enhancer, hence driving UCP1 transcription. Overall, our study defines the role of CIDEA in increasing thermogenesis in human adipocytes. Elsevier 2019-09-13 /pmc/articles/PMC6817690/ /pubmed/31563853 http://dx.doi.org/10.1016/j.isci.2019.09.011 Text en © 2019 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Jash, Sukanta
Banerjee, Sayani
Lee, Mi-Jeong
Farmer, Stephen R.
Puri, Vishwajeet
CIDEA Transcriptionally Regulates UCP1 for Britening and Thermogenesis in Human Fat Cells
title CIDEA Transcriptionally Regulates UCP1 for Britening and Thermogenesis in Human Fat Cells
title_full CIDEA Transcriptionally Regulates UCP1 for Britening and Thermogenesis in Human Fat Cells
title_fullStr CIDEA Transcriptionally Regulates UCP1 for Britening and Thermogenesis in Human Fat Cells
title_full_unstemmed CIDEA Transcriptionally Regulates UCP1 for Britening and Thermogenesis in Human Fat Cells
title_short CIDEA Transcriptionally Regulates UCP1 for Britening and Thermogenesis in Human Fat Cells
title_sort cidea transcriptionally regulates ucp1 for britening and thermogenesis in human fat cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6817690/
https://www.ncbi.nlm.nih.gov/pubmed/31563853
http://dx.doi.org/10.1016/j.isci.2019.09.011
work_keys_str_mv AT jashsukanta cideatranscriptionallyregulatesucp1forbriteningandthermogenesisinhumanfatcells
AT banerjeesayani cideatranscriptionallyregulatesucp1forbriteningandthermogenesisinhumanfatcells
AT leemijeong cideatranscriptionallyregulatesucp1forbriteningandthermogenesisinhumanfatcells
AT farmerstephenr cideatranscriptionallyregulatesucp1forbriteningandthermogenesisinhumanfatcells
AT purivishwajeet cideatranscriptionallyregulatesucp1forbriteningandthermogenesisinhumanfatcells