Lack of activation of UCP1 in isolated brown adipose tissue mitochondria by glucose-O-?-modified saturated fatty acids of various chain lengths.

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-?-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-?-fatty acids to activate uncoupling protein 1. Glucose-O-?-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-?-laurate (12C), glucose-O-?-palmitate (16C), glucose-O-?-stearate (18C), glucose-O-?-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.

SUBMITTER: Breen EP 

PROVIDER: S-EPMC3691397 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature