Universität zu Köln

van Weeghel, Michel ORCID: 0000-0002-4916-2866, te Brinke, Heleen, van Lenthe, Henk, Kulik, Wim, Minkler, Paul E., Stoll, Maria S. K., Sass, Joern Oliver, Janssen, Uwe, Stoffel, Wilhelm, Schwab, K. Otfried, Wanders, Ronald J. A., Hoppel, Charles L. and Houten, Sander M. (2012). Functional redundancy of mitochondrial enoyl-CoA isomerases in the oxidation of unsaturated fatty acids. Faseb J., 26 (10). S. 4316 - 4327. BETHESDA: FEDERATION AMER SOC EXP BIOL. ISSN 0892-6638

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Abstract

Mitochondrial enoyl-CoA isomerase (ECI1) is an auxiliary enzyme involved in unsaturated fatty acid oxidation. In contrast to most of the other enzymes involved in fatty acid oxidation, a deficiency of ECI1 has yet to be identified in humans. We used wild-type (WT) and Eci1-deficient knockout (KO) mice to explore a potential presentation of human ECI1 deficiency. Upon food withdrawal, Eci1-deficient mice displayed normal blood beta-hydroxybutyrate levels (WT 1.09 mM vs. KO 1.10 mM), a trend to lower blood glucose levels (WT 4.58 mM vs. KO 3.87 mM, P=0.09) and elevated blood levels of unsaturated acylcarnitines, in particular C12:1 acylcarnitine (WT 0.03 mu M vs. KO 0.09 mu M, P<0.01). Feeding an olive oil-rich diet induced an even greater increase in C12: 1 acylcarnitine levels (WT 0.01 mu M vs. KO 0.04 mu M, P<0.01). Overall, the phenotypic presentation of Eci1-deficient mice is mild, possibly caused by the presence of a second enoyl-CoA isomerase (Eci2) in mitochondria. Knockdown of Eci2 in Eci1-deficient fibroblasts caused a more pronounced accumulation of C12: 1 acylcarnitine on incubation with unsaturated fatty acids (12-fold, P<0.05). We conclude that Eci2 compensates for Eci1 deficiency explaining the mild phenotype of Eci1-deficient mice. Hypoglycemia and accumulation of C12: 1 acylcarnitine might be diagnostic markers to identify ECI1 deficiency in humans.-van Weeghel, M., te Brinke, H., van Lenthe, H., Kulik, W., Minkler, P. E., Stoll, M. S. K., Sass, J. O., Janssen, U., Stoffel, W., Schwab, O. K., Wanders, R. J. A., Hoppel, C. L., Houten, S. M. Functional redundancy of mitochondrial enoyl-CoA isomerases in the oxidation of unsaturated fatty acids. FASEB J. 26, 4316-4326 (2012). www.fasebj.org

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code van Weeghel, Michel UNSPECIFIED orcid.org/0000-0002-4916-2866 UNSPECIFIED te Brinke, Heleen UNSPECIFIED UNSPECIFIED UNSPECIFIED van Lenthe, Henk UNSPECIFIED UNSPECIFIED UNSPECIFIED Kulik, Wim UNSPECIFIED UNSPECIFIED UNSPECIFIED Minkler, Paul E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Stoll, Maria S. K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sass, Joern Oliver UNSPECIFIED UNSPECIFIED UNSPECIFIED Janssen, Uwe UNSPECIFIED UNSPECIFIED UNSPECIFIED Stoffel, Wilhelm UNSPECIFIED UNSPECIFIED UNSPECIFIED Schwab, K. Otfried UNSPECIFIED UNSPECIFIED UNSPECIFIED Wanders, Ronald J. A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoppel, Charles L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Houten, Sander M. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-481514
DOI:	10.1096/fj.12-206326
Journal or Publication Title:	Faseb J.
Volume:	26
Number:	10
Page Range:	S. 4316 - 4327
Date:	2012
Publisher:	FEDERATION AMER SOC EXP BIOL
Place of Publication:	BETHESDA
ISSN:	0892-6638
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language TANDEM MASS-SPECTROMETRY; BETA-OXIDATION; RAT-LIVER; DELTA-3,DELTA-2-ENOYL-COA ISOMERASE; 3-HYDROXYACYL-COA DEHYDROGENASE; 2-ENOYL-COA HYDRATASE; ZELLWEGER SYNDROME; ENZYME; MOUSE; FIBROBLASTS Multiple languages Biochemistry & Molecular Biology; Biology; Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/48151