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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.* ; Heeren, J.* ; Scheja, L.*

Endogenous fatty acid synthesis drives brown adipose tissue involution.

Cell Rep. 34:108624 (2021)
Postprint Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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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Publication type Article: Journal article
Document type Scientific Article
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; Element-binding Protein; Diet-induced Thermogenesis; De-novo Lipogenesis; Cardiolipin; Autophagy; Inhibitors; Mice; Ucp1; Physiology; Humans
Language english
Publication Year 2021
HGF-reported in Year 2021
ISSN (print) / ISBN 2211-1247
e-ISSN 2211-1247
Journal Cell Reports
Quellenangaben Volume: 34, Issue: 2, Pages: , Article Number: 108624 Supplement: ,
Publisher Cell Press
Publishing Place 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes and Cancer (IDC)
POF-Topic(s) 90000 - German Center for Diabetes Research
Research field(s) Helmholtz Diabetes Center
PSP Element(s) G-501900-251
Grants Christine-KatharinaSchmitz-Foundation
Gertraud and Heinz Rose Foundation
UKE MD/PhD program fellowship
German National Academic Foundation
DFG
DACH Gesellschaft f_ur Lipidologie
Deutsches Zentrum fur Herz-Kreislauf-Forschung Junior Research Group grant
Danish Diabetes Academy - Novo Nordisk Foundation
TrygFonden
Deutsche Forschungsgemeinschaft
DOI 10.1016/j.celrep.2020.108624
WOS ID WOS:000607913800021
Scopus ID 85099160502
PubMed ID 33440156
Erfassungsdatum 2021-03-26
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