Endogenous Fatty Acid Synthesis Drives Brown Adipose Tissue Involution

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

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.

In: Cell Reports, Vol. 34, No. 2, 108624, 2021.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Schlein, C, Fischer, AW, Sass, F, Worthmann, A, Tödter, K, Jaeckstein, MY, Behrens, J, Lynes, MD, Kiebish, MA, Narain, NR, Bussberg, V, Darkwah, A, Jespersen, NZ, Nielsen, S, Scheele, C, Schweizer, M, Braren, I, Bartelt, A, Tseng, YH, Heeren, J & Scheja, L 2021, 'Endogenous Fatty Acid Synthesis Drives Brown Adipose Tissue Involution', Cell Reports, vol. 34, no. 2, 108624. https://doi.org/10.1016/j.celrep.2020.108624

APA

Schlein, C., Fischer, A. W., Sass, F., Worthmann, A., Tödter, K., Jaeckstein, M. Y., Behrens, J., Lynes, M. D., Kiebish, M. A., Narain, N. R., Bussberg, V., Darkwah, A., Jespersen, N. Z., Nielsen, S., Scheele, C., Schweizer, M., Braren, I., Bartelt, A., Tseng, Y. H., ... Scheja, L. (2021). Endogenous Fatty Acid Synthesis Drives Brown Adipose Tissue Involution. Cell Reports, 34(2), [108624]. https://doi.org/10.1016/j.celrep.2020.108624

Vancouver

Schlein C, Fischer AW, Sass F, Worthmann A, Tödter K, Jaeckstein MY et al. Endogenous Fatty Acid Synthesis Drives Brown Adipose Tissue Involution. Cell Reports. 2021;34(2). 108624. https://doi.org/10.1016/j.celrep.2020.108624

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. / Endogenous Fatty Acid Synthesis Drives Brown Adipose Tissue Involution. In: Cell Reports. 2021 ; Vol. 34, No. 2.

Bibtex

@article{508ce88daa424574b03922970d4861d8,
title = "Endogenous Fatty Acid Synthesis Drives Brown Adipose Tissue Involution",
abstract = "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.",
keywords = "brown adipose tissue, cardiolipins, ChREBP, de novo lipogenesis, energy expenditure, fatty acid synthesis, fatty acids, lipidome, mitochondria, mitophagy, non-shivering thermogenesis, phospholipids, thermoneutrality, triacylglycerols, whitening",
author = "Christian Schlein and Fischer, {Alexander W.} and Frederike Sass and Anna Worthmann and Klaus T{\"o}dter and Jaeckstein, {Michelle Y.} and Janina Behrens and Lynes, {Matthew D.} and Kiebish, {Michael A.} and Narain, {Niven R.} and Val Bussberg and Abena Darkwah and Jespersen, {Naja Zenius} and S{\o}ren Nielsen and Camilla Scheele and Michaela Schweizer and Ingke Braren and Alexander Bartelt and Tseng, {Yu Hua} and Joerg Heeren and Ludger Scheja",
year = "2021",
doi = "10.1016/j.celrep.2020.108624",
language = "English",
volume = "34",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "2",

}

RIS

TY - JOUR

T1 - Endogenous Fatty Acid Synthesis Drives Brown Adipose Tissue Involution

AU - Schlein, Christian

AU - Fischer, Alexander W.

AU - Sass, Frederike

AU - Worthmann, Anna

AU - Tödter, Klaus

AU - Jaeckstein, Michelle Y.

AU - Behrens, Janina

AU - Lynes, Matthew D.

AU - Kiebish, Michael A.

AU - Narain, Niven R.

AU - Bussberg, Val

AU - Darkwah, Abena

AU - Jespersen, Naja Zenius

AU - Nielsen, Søren

AU - Scheele, Camilla

AU - Schweizer, Michaela

AU - Braren, Ingke

AU - Bartelt, Alexander

AU - Tseng, Yu Hua

AU - Heeren, Joerg

AU - Scheja, Ludger

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

KW - brown adipose tissue

KW - cardiolipins

KW - ChREBP

KW - de novo lipogenesis

KW - energy expenditure

KW - fatty acid synthesis

KW - fatty acids

KW - lipidome

KW - mitochondria

KW - mitophagy

KW - non-shivering thermogenesis

KW - phospholipids

KW - thermoneutrality

KW - triacylglycerols

KW - whitening

U2 - 10.1016/j.celrep.2020.108624

DO - 10.1016/j.celrep.2020.108624

M3 - Journal article

C2 - 33440156

AN - SCOPUS:85099160502

VL - 34

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 2

M1 - 108624

ER -

ID: 256326876