Cold-induction of afadin in brown fat supports its thermogenic capacity

Abstract The profound energy-expending nature of brown adipose tissue (BAT) thermogenesis makes it an attractive target tissue to combat obesity-associated metabolic disorders. While cold exposure is the strongest inducer of BAT activity, the temporal mechanisms tuning BAT adaptation during this act...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Morten Lundh, Ali Altıntaş, Marco Tozzi, Odile Fabre, Tao Ma, Farnaz Shamsi, Zachary Gerhart-Hines, Romain Barrès, Yu-Hua Tseng, Brice Emanuelli
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d7c56c917a264bc39cc895ee89f8c7c9
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:d7c56c917a264bc39cc895ee89f8c7c9
record_format	dspace
spelling	oai:doaj.org-article:d7c56c917a264bc39cc895ee89f8c7c92021-12-02T14:49:25ZCold-induction of afadin in brown fat supports its thermogenic capacity10.1038/s41598-021-89207-22045-2322https://doaj.org/article/d7c56c917a264bc39cc895ee89f8c7c92021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89207-2https://doaj.org/toc/2045-2322Abstract The profound energy-expending nature of brown adipose tissue (BAT) thermogenesis makes it an attractive target tissue to combat obesity-associated metabolic disorders. While cold exposure is the strongest inducer of BAT activity, the temporal mechanisms tuning BAT adaptation during this activation process are incompletely understood. Here we show that the scaffold protein Afadin is dynamically regulated by cold in BAT, and participates in cold acclimation. Cold exposure acutely increases Afadin protein levels and its phosphorylation in BAT. Knockdown of Afadin in brown pre-adipocytes does not alter adipogenesis but restricts β3-adrenegic induction of thermogenic genes expression and HSL phosphorylation in mature brown adipocytes. Consistent with a defect in thermogenesis, an impaired cold tolerance was observed in fat-specific Afadin knockout mice. However, while Afadin depletion led to reduced Ucp1 mRNA induction by cold, stimulation of Ucp1 protein was conserved. Transcriptomic analysis revealed that fat-specific ablation of Afadin led to decreased functional enrichment of gene sets controlling essential metabolic functions at thermoneutrality in BAT, whereas it led to an altered reprogramming in response to cold, with enhanced enrichment of different pathways related to metabolism and remodeling. Collectively, we demonstrate a role for Afadin in supporting the adrenergic response in brown adipocytes and BAT function.Morten LundhAli AltıntaşMarco TozziOdile FabreTao MaFarnaz ShamsiZachary Gerhart-HinesRomain BarrèsYu-Hua TsengBrice EmanuelliNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Morten Lundh Ali Altıntaş Marco Tozzi Odile Fabre Tao Ma Farnaz Shamsi Zachary Gerhart-Hines Romain Barrès Yu-Hua Tseng Brice Emanuelli Cold-induction of afadin in brown fat supports its thermogenic capacity
description	Abstract The profound energy-expending nature of brown adipose tissue (BAT) thermogenesis makes it an attractive target tissue to combat obesity-associated metabolic disorders. While cold exposure is the strongest inducer of BAT activity, the temporal mechanisms tuning BAT adaptation during this activation process are incompletely understood. Here we show that the scaffold protein Afadin is dynamically regulated by cold in BAT, and participates in cold acclimation. Cold exposure acutely increases Afadin protein levels and its phosphorylation in BAT. Knockdown of Afadin in brown pre-adipocytes does not alter adipogenesis but restricts β3-adrenegic induction of thermogenic genes expression and HSL phosphorylation in mature brown adipocytes. Consistent with a defect in thermogenesis, an impaired cold tolerance was observed in fat-specific Afadin knockout mice. However, while Afadin depletion led to reduced Ucp1 mRNA induction by cold, stimulation of Ucp1 protein was conserved. Transcriptomic analysis revealed that fat-specific ablation of Afadin led to decreased functional enrichment of gene sets controlling essential metabolic functions at thermoneutrality in BAT, whereas it led to an altered reprogramming in response to cold, with enhanced enrichment of different pathways related to metabolism and remodeling. Collectively, we demonstrate a role for Afadin in supporting the adrenergic response in brown adipocytes and BAT function.
format	article
author	Morten Lundh Ali Altıntaş Marco Tozzi Odile Fabre Tao Ma Farnaz Shamsi Zachary Gerhart-Hines Romain Barrès Yu-Hua Tseng Brice Emanuelli
author_facet	Morten Lundh Ali Altıntaş Marco Tozzi Odile Fabre Tao Ma Farnaz Shamsi Zachary Gerhart-Hines Romain Barrès Yu-Hua Tseng Brice Emanuelli
author_sort	Morten Lundh
title	Cold-induction of afadin in brown fat supports its thermogenic capacity
title_short	Cold-induction of afadin in brown fat supports its thermogenic capacity
title_full	Cold-induction of afadin in brown fat supports its thermogenic capacity
title_fullStr	Cold-induction of afadin in brown fat supports its thermogenic capacity
title_full_unstemmed	Cold-induction of afadin in brown fat supports its thermogenic capacity
title_sort	cold-induction of afadin in brown fat supports its thermogenic capacity
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d7c56c917a264bc39cc895ee89f8c7c9
work_keys_str_mv	AT mortenlundh coldinductionofafadininbrownfatsupportsitsthermogeniccapacity AT alialtıntas coldinductionofafadininbrownfatsupportsitsthermogeniccapacity AT marcotozzi coldinductionofafadininbrownfatsupportsitsthermogeniccapacity AT odilefabre coldinductionofafadininbrownfatsupportsitsthermogeniccapacity AT taoma coldinductionofafadininbrownfatsupportsitsthermogeniccapacity AT farnazshamsi coldinductionofafadininbrownfatsupportsitsthermogeniccapacity AT zacharygerharthines coldinductionofafadininbrownfatsupportsitsthermogeniccapacity AT romainbarres coldinductionofafadininbrownfatsupportsitsthermogeniccapacity AT yuhuatseng coldinductionofafadininbrownfatsupportsitsthermogeniccapacity AT briceemanuelli coldinductionofafadininbrownfatsupportsitsthermogeniccapacity
_version_	1718389479396343808

Cold-induction of afadin in brown fat supports its thermogenic capacity

Ejemplares similares