TY  - JOUR
U1  - Zeitschriftenartikel, wissenschaftlich - begutachtet (reviewed)
A1  - van Weeghel, Michel
A1  - te Brinke, Heleen
A1  - van Lenthe, Henk
A1  - Kulik, Wim
A1  - Minkler, Paul E.
A1  - Stoll, Maria S. K.
A1  - Sass, Jörn Oliver
A1  - Janssen, Uwe
A1  - Stoffel, Wilhelm
A1  - Schwab, K. Otfried
A1  - Wanders, Ronald J. A.
A1  - Hoppel, Charles L.
A1  - Houten, Sander M.
T1  - Functional redundancy of mitochondrial enoyl-CoA isomerases in the oxidation of unsaturated fatty acids
JF  - FASEB J. (FASEB Journal)
N2  - 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 β-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 μM vs. KO 0.09 μM, P<0.01). Feeding an olive oil-rich diet induced an even greater increase in C12:1 acylcarnitine levels (WT 0.01 μM vs. KO 0.04 μM, 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.
Y1  - 2012
SN  - 0892-6638
SS  - 0892-6638
U6  - https://doi.org/10.1096/fj.12-206326
DO  - https://doi.org/10.1096/fj.12-206326
PM  - 22782973
VL  - 26
IS  - 10
SP  - 4316
EP  - 4326
ER  -