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Endogenous Fatty Acid Synthesis Drives Brown Adipose Tissue Involution

Thermoneutral conditions typical for standard human living environments result in brown adipose tissue (BAT) involution, characterized by decreased mitochondrial mass and increased lipid deposition. Low BAT activity is associated with poor metabolic health, and BAT reactivation may confer therapeuti...

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Autores principales: Schlein, Christian, Fischer, Alexander W., Sass, Frederike, Worthmann, Anna, Tödter, Klaus, Jaeckstein, Michelle Y., Behrens, Janina, Lynes, Matthew D., Kiebish, Michael A., Narain, Niven R., Bussberg, Val, Darkwah, Abena, Jespersen, Naja Zenius, Nielsen, Søren, Scheele, Camilla, Schweizer, Michaela, Braren, Ingke, Bartelt, Alexander, Tseng, Yu-Hua, Heeren, Joerg, Scheja, Ludger
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240962/
https://www.ncbi.nlm.nih.gov/pubmed/33440156
http://dx.doi.org/10.1016/j.celrep.2020.108624
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author Schlein, Christian
Fischer, Alexander W.
Sass, Frederike
Worthmann, Anna
Tödter, Klaus
Jaeckstein, Michelle Y.
Behrens, Janina
Lynes, Matthew D.
Kiebish, Michael A.
Narain, Niven R.
Bussberg, Val
Darkwah, Abena
Jespersen, Naja Zenius
Nielsen, Søren
Scheele, Camilla
Schweizer, Michaela
Braren, Ingke
Bartelt, Alexander
Tseng, Yu-Hua
Heeren, Joerg
Scheja, Ludger
author_facet Schlein, Christian
Fischer, Alexander W.
Sass, Frederike
Worthmann, Anna
Tödter, Klaus
Jaeckstein, Michelle Y.
Behrens, Janina
Lynes, Matthew D.
Kiebish, Michael A.
Narain, Niven R.
Bussberg, Val
Darkwah, Abena
Jespersen, Naja Zenius
Nielsen, Søren
Scheele, Camilla
Schweizer, Michaela
Braren, Ingke
Bartelt, Alexander
Tseng, Yu-Hua
Heeren, Joerg
Scheja, Ludger
author_sort Schlein, Christian
collection PubMed
description Thermoneutral conditions typical for standard human living environments result in brown adipose tissue (BAT) involution, characterized by decreased mitochondrial mass and increased lipid deposition. Low BAT activity is associated with poor metabolic health, and BAT reactivation may confer therapeutic potential. However, the molecular drivers of this BAT adaptive process in response to thermoneutrality remain enigmatic. Using metabolic and lipidomic approaches, we show that endogenous fatty acid synthesis, regulated by carbohydrate-response element-binding protein (ChREBP), is the central regulator of BAT involution. By transcriptional control of lipogenesis-related enzymes, ChREBP determines the abundance and composition of both storage and membrane lipids known to regulate organelle turnover and function. Notably, ChREBP deficiency and pharmacological inhibition of lipogenesis during thermoneutral adaptation preserved mitochondrial mass and thermogenic capacity of BAT independently of mitochondrial biogenesis. In conclusion, we establish lipogenesis as a potential therapeutic target to prevent loss of BAT thermogenic capacity as seen in adult humans.
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spelling pubmed-82409622021-06-29 Endogenous Fatty Acid Synthesis Drives Brown Adipose Tissue Involution Schlein, Christian Fischer, Alexander W. Sass, Frederike Worthmann, Anna Tödter, Klaus Jaeckstein, Michelle Y. Behrens, Janina Lynes, Matthew D. Kiebish, Michael A. Narain, Niven R. Bussberg, Val Darkwah, Abena Jespersen, Naja Zenius Nielsen, Søren Scheele, Camilla Schweizer, Michaela Braren, Ingke Bartelt, Alexander Tseng, Yu-Hua Heeren, Joerg Scheja, Ludger Cell Rep Article Thermoneutral conditions typical for standard human living environments result in brown adipose tissue (BAT) involution, characterized by decreased mitochondrial mass and increased lipid deposition. Low BAT activity is associated with poor metabolic health, and BAT reactivation may confer therapeutic potential. However, the molecular drivers of this BAT adaptive process in response to thermoneutrality remain enigmatic. Using metabolic and lipidomic approaches, we show that endogenous fatty acid synthesis, regulated by carbohydrate-response element-binding protein (ChREBP), is the central regulator of BAT involution. By transcriptional control of lipogenesis-related enzymes, ChREBP determines the abundance and composition of both storage and membrane lipids known to regulate organelle turnover and function. Notably, ChREBP deficiency and pharmacological inhibition of lipogenesis during thermoneutral adaptation preserved mitochondrial mass and thermogenic capacity of BAT independently of mitochondrial biogenesis. In conclusion, we establish lipogenesis as a potential therapeutic target to prevent loss of BAT thermogenic capacity as seen in adult humans. 2021-01-12 /pmc/articles/PMC8240962/ /pubmed/33440156 http://dx.doi.org/10.1016/j.celrep.2020.108624 Text en https://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/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ).
spellingShingle Article
Schlein, Christian
Fischer, Alexander W.
Sass, Frederike
Worthmann, Anna
Tödter, Klaus
Jaeckstein, Michelle Y.
Behrens, Janina
Lynes, Matthew D.
Kiebish, Michael A.
Narain, Niven R.
Bussberg, Val
Darkwah, Abena
Jespersen, Naja Zenius
Nielsen, Søren
Scheele, Camilla
Schweizer, Michaela
Braren, Ingke
Bartelt, Alexander
Tseng, Yu-Hua
Heeren, Joerg
Scheja, Ludger
Endogenous Fatty Acid Synthesis Drives Brown Adipose Tissue Involution
title Endogenous Fatty Acid Synthesis Drives Brown Adipose Tissue Involution
title_full Endogenous Fatty Acid Synthesis Drives Brown Adipose Tissue Involution
title_fullStr Endogenous Fatty Acid Synthesis Drives Brown Adipose Tissue Involution
title_full_unstemmed Endogenous Fatty Acid Synthesis Drives Brown Adipose Tissue Involution
title_short Endogenous Fatty Acid Synthesis Drives Brown Adipose Tissue Involution
title_sort endogenous fatty acid synthesis drives brown adipose tissue involution
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240962/
https://www.ncbi.nlm.nih.gov/pubmed/33440156
http://dx.doi.org/10.1016/j.celrep.2020.108624
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