Universität zu Köln

Duteil, Delphine ORCID: 0000-0001-5826-0153, Metzger, Eric, Willmann, Dominica, Karagianni, Panagiota, Friedrichs, Nicolaus, Greschik, Holger, Guenther, Thomas, Buettner, Reinhard, Talianidis, Iannis ORCID: 0000-0002-1209-3609, Metzger, Daniel ORCID: 0000-0002-5555-046X and Schuele, Roland (2014). LSD1 promotes oxidative metabolism of white adipose tissue. Nat. Commun., 5. LONDON: NATURE PUBLISHING GROUP. ISSN 2041-1723

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Abstract

Exposure to environmental cues such as cold or nutritional imbalance requires white adipose tissue (WAT) to adapt its metabolism to ensure survival. Metabolic plasticity is prominently exemplified by the enhancement of mitochondrial biogenesis in WAT in response to cold exposure or b3-adrenergic stimulation. Here we show that these stimuli increase the levels of lysine-specific demethylase 1 (LSD1) in WAT of mice and that elevated LSD1 levels induce mitochondrial activity. Genome-wide binding and transcriptome analyses demonstrate that LSD1 directly stimulates the expression of genes involved in oxidative phosphorylation (OXPHOS) in cooperation with nuclear respiratory factor 1 (Nrf1). In transgenic (Tg) mice, increased levels of LSD1 promote in a cell-autonomous manner the formation of islets of metabolically active brown-like adipocytes in WAT. Notably, Tg mice show limited weight gain when fed a high-fat diet. Taken together, our data establish LSD1 as a key regulator of OXPHOS and metabolic adaptation in WAT.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Duteil, Delphine UNSPECIFIED orcid.org/0000-0001-5826-0153 UNSPECIFIED Metzger, Eric UNSPECIFIED UNSPECIFIED UNSPECIFIED Willmann, Dominica UNSPECIFIED UNSPECIFIED UNSPECIFIED Karagianni, Panagiota UNSPECIFIED UNSPECIFIED UNSPECIFIED Friedrichs, Nicolaus UNSPECIFIED UNSPECIFIED UNSPECIFIED Greschik, Holger UNSPECIFIED UNSPECIFIED UNSPECIFIED Guenther, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Buettner, Reinhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Talianidis, Iannis UNSPECIFIED orcid.org/0000-0002-1209-3609 UNSPECIFIED Metzger, Daniel UNSPECIFIED orcid.org/0000-0002-5555-046X UNSPECIFIED Schuele, Roland UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-436395
DOI:	10.1038/ncomms5093
Journal or Publication Title:	Nat. Commun.
Volume:	5
Date:	2014
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2041-1723
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language BROWN FAT; MITOCHONDRIAL BIOGENESIS; TRANSCRIPTIONAL CONTROL; EXPRESSION ANALYSIS; INSULIN-RESISTANCE; ENERGY-BALANCE; ADIPOCYTES; CELLS; GENE; THERMOGENESIS Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/43639