Universität zu Köln

Hammels, Ina, Binczek, Erika, Schmidt-Soltau, Inga, Jenke, Britta, Thomas, Andreas ORCID: 0000-0003-1199-0743, Vogel, Matthias, Thevis, Mario, Filipova, Dilyana, Papadopoulos, Symeon and Stoffel, Wilhelm (2019). Novel CB1-ligands maintain homeostasis of the endocannabinoid system in omega 3-and omega 6-long-chain-PUFA deficiency[S]. J. Lipid Res., 60 (8). S. 1396 - 1410. ROCKVILLE: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC. ISSN 1539-7262

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Abstract

Mammalian omega 3- and omega 6-PUFAs are synthesized from essential fatty acids (EFAs) or supplied by the diet. PUFAs are constitutive elements of membrane architecture and precursors of lipid signaling molecules. EFAs and long-chain (LC)-PUFAs are precursors in the synthesis of endocannabinoid ligands of G(i/o) protein-coupled cannabinoid receptor (CB)1 and CB2 in the endocannabinoid system, which critically regulate energy homeostasis as the metabolic signaling system in hypothalamic neuronal circuits and behavioral parameters. We utilized the auxotrophic fatty acid desaturase 2-deficient (fads2(-/-)) mouse, deficient in LC-PUFA synthesis, to follow the age-dependent dynamics of the PUFA pattern in the CNS-phospholipidome in unbiased dietary studies of three cohorts on sustained LC-PUFA-free omega 6-arachidonic acid- and DHA-supplemented diets and their impact on the precursor pool of CB1 ligands. We discovered the transformation of eicosa-all cis-5,11,14-trienoic acid, uncommon in mammalian lipidomes, into two novel endocannabinoids, 20:3(5,11,14)-ethanolamide and 2-20:3(5,11,14)-glycerol. Their function as ligands of CB1 has been characterized in HEK293 cells. Labeling experiments excluded Delta 8-desaturase activity and proved the position specificity of FADS2. The fads2(-/-) mutant might serve as an unbiased model in vivo in the development of novel CB1 agonists and antagonists.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hammels, Ina UNSPECIFIED UNSPECIFIED UNSPECIFIED Binczek, Erika UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmidt-Soltau, Inga UNSPECIFIED UNSPECIFIED UNSPECIFIED Jenke, Britta UNSPECIFIED UNSPECIFIED UNSPECIFIED Thomas, Andreas UNSPECIFIED orcid.org/0000-0003-1199-0743 UNSPECIFIED Vogel, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Thevis, Mario UNSPECIFIED UNSPECIFIED UNSPECIFIED Filipova, Dilyana UNSPECIFIED UNSPECIFIED UNSPECIFIED Papadopoulos, Symeon UNSPECIFIED UNSPECIFIED UNSPECIFIED Stoffel, Wilhelm UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-145227
DOI:	10.1194/jlr.M094664
Journal or Publication Title:	J. Lipid Res.
Volume:	60
Number:	8
Page Range:	S. 1396 - 1410
Date:	2019
Publisher:	AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Place of Publication:	ROCKVILLE
ISSN:	1539-7262
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language POLYUNSATURATED FATTY-ACIDS; RETINOID-X-RECEPTOR; CANNABINOID RECEPTOR; DOCOSAHEXAENOIC ACID; CARDIOVASCULAR-DISEASE; FADS2 GENE; ANANDAMIDE; BRAIN; LIGAND; N-3 Multiple languages Biochemistry & Molecular Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/14522