Lack of activation of UCP1 in isolated brown adipose tissue mitochondria by glucose-O-ω-modified saturated fatty acids of various chain lengths.
Citation:
Breen EP, Pilgrim W, Clarke KJ, Yssel C, Farrell M, Zhou J, Murphy PV, Porter RK. , Lack of activation of UCP1 in isolated brown adipose tissue mitochondria by glucose-O-ω-modified saturated fatty acids of various chain lengths., Journal of Chemical Biology, 6, 3, 2013, 121 - 133Download Item:
12154_2013_Article_93.pdf (PDF) 528.1Kb
Abstract:
We previously demonstrated that uncoupling protein 1 activity, as measured in isolated brown adipose tissue mitochondria (and as a native protein reconstituted into liposome membranes), was not activated by the non-flippable modified saturated fatty acid, glucose-O-ω-palmitate, whereas activity was stimulated by palmitate alone (40 nM free final concentration). In this study, we investigated whether fatty acid chain length had any bearing on the ability of glucose-O-ω-fatty acids to activate uncoupling protein 1. Glucose-O-ω-saturated fatty acids of various chain lengths were synthesized and tested for their potential to activate GDP-inhibited uncoupling protein 1-dependent oxygen consumption in brown adipose tissue mitochondria, and the results were compared with equivalent non-modified fatty acid controls. Here we demonstrate that laurate (12C), palmitate (16C) and stearate (18C) could activate GDP-inhibited uncoupling protein 1-dependent oxygen consumption in brown adipose tissue mitochondria, whereas there was no activation with glucose-O-ω-laurate (12C), glucose-O-ω-palmitate (16C), glucose-O-ω-stearate (18C), glucose-O-ω-arachidate (20C) or arachidate alone. We conclude that non-flippable fatty acids cannot activate uncoupling protein 1 irrespective of chain length. Our data further undermine the cofactor activation model of uncoupling protein 1 function but are compatible with the model that uncoupling protein 1 functions by flipping long-chain fatty acid anions.
Sponsor
Grant Number
Marie Curie
Science Foundation Ireland (SFI)
Author's Homepage:
http://people.tcd.ie/rkporterDescription:
PUBLISHED
Author: Porter, Richard
Type of material:
Journal ArticleCollections:
Series/Report no:
Journal of Chemical Biology6
3
Availability:
Full text availableKeywords:
UCP1, Mitochondria, Glucose-O-ω-fatty acids, BATSubject (TCD):
Immunology, Inflammation & Infection , Biochemistry, metabolismLicences: