Endogenous Fatty Acid Synthesis Drives Brown Adipose Tissue Involution
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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
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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