Universität zu Köln

Stoffel, Wilhelm, Hammels, Ina, Jenke, Britta, Binczek, Erika, Schmidt-Soltau, Inga, Brodesser, Susanne, Odenthal, Margarete and Thevis, Mario (2014). Obesity resistance and deregulation of lipogenesis in Delta 6-fatty acid desaturase (FADS2) deficiency. EMBO Rep., 15 (1). S. 110 - 121. HOBOKEN: WILEY. ISSN 1469-3178

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Abstract

Delta-6-fatty acid desaturase (FADS2) is the key enzyme in the biosynthesis of polyunsaturated fatty acids (PUFAs), the essential structural determinants of mammalian membrane lipid-bilayers. We developed the auxotrophic fads2(-/-) mouse mutant to assess the enigmatic role of omega 3- and omega 6-PUFAs in lipid homeostasis, membrane structure and function. Obesity resistance is another major phenotype of the fads2(-/-) mutant, the molecular basis of which is unknown. Phospholipidomic profiling of membrane systems of fads2(-/-) mice revealed diacylglycerol-structures, deprived of PUFAs but substituted with surrogate eicosa-5,11,14-trienoic acid. omega 6-Arachidonic (AA) and omega 3-docosahexaenoic acid (DHA) supplemented diets transformed fads2(-/-) into AA-fads2(-/-) and DHA-fads2(-/-) mutants. Severely altered phospholipid-bilayer structures of subcellular membranes of fads2(-/-) liver specifically interfered with maturation of transcription factor sterol-regulatory-element-binding protein, the key regulator of lipogenesis and lipid homeostasis. This study strengthens the concept that specific PUFA-substituted membrane phospholipid species are critical constituents of the structural platform operative in lipid homeostasis in normal and disease conditions.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Stoffel, Wilhelm UNSPECIFIED UNSPECIFIED UNSPECIFIED Hammels, Ina UNSPECIFIED UNSPECIFIED UNSPECIFIED Jenke, Britta UNSPECIFIED UNSPECIFIED UNSPECIFIED Binczek, Erika UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmidt-Soltau, Inga UNSPECIFIED UNSPECIFIED UNSPECIFIED Brodesser, Susanne UNSPECIFIED UNSPECIFIED UNSPECIFIED Odenthal, Margarete UNSPECIFIED UNSPECIFIED UNSPECIFIED Thevis, Mario UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-451305
DOI:	10.1002/embr.201338041
Journal or Publication Title:	EMBO Rep.
Volume:	15
Number:	1
Page Range:	S. 110 - 121
Date:	2014
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1469-3178
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language POLYUNSATURATED FATTY-ACIDS; MASS-SPECTROMETRY; BIOSYNTHESIS; DERIVATIVES; EXPRESSION Multiple languages Biochemistry & Molecular Biology; Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/45130