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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)
Verlagsversion Forschungsdaten 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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter 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
ISSN (print) / ISBN 2211-1247
e-ISSN 2211-1247
Zeitschrift Cell Reports
Quellenangaben Band: 34, Heft: 2, Seiten: , Artikelnummer: 108624 Supplement: ,
Verlag Cell Press
Verlagsort 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Cancer (IDC)
Förderungen 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