Shabalina 2015 Abstract MiP2015
|The metabolically inert environmental pollutants perfluorinated fatty acids directly activate uncoupling protein 1 in brown-fat mitochondria.
The environmental pollutants perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are degradation products of polyfluorinated surfactants and polymers that due to their unique surface-active properties, the stability of their C-F bonds and their thermal resistivity, are utilized in a wide variety of products, including fire-fighting foams, lubricants, paints, cosmetics and ski-wax. PFOS/PFOA cause a dramatic reduction in the size of the major adipose tissue depots when they are added to the food of mice. A large part of the effect of PFOA/PFOS on food intake was dependent on the presence of the uncoupling protein 1 (UCP1) in the brown adipose tissue .
We have examined here the possibility that PFOA/PFOS can directly (re)activate UCP1 in isolated mouse brown-fat mitochondria. In wildtype brown-fat mitochondria, PFOS and PFOA overcame GDP-inhibited thermogenesis, leading to increased oxygen consumption and dissipated membrane potential. The absence of this effect in brown-fat mitochondria from UCP1-ablated mice indicated that it occurred through activation of UCP1. A competitive type of inhibition by increased GDP concentrations indicated interaction with the same mechanistic site as that utilized by fatty acids. The stimulatory effect of PFOA/PFOS was not secondary to nonspecific mitochondrial membrane permeabilisation or to ROS production.
Thus, metabolic effects of perfluorinated fatty acids could include direct brown adipose tissue (UCP1) activation. The possibility that this may lead to unwarranted extra heat production and thus extra utilization of food resources, leading to decreased fitness in mammalian wildlife, is discussed, as well as possible negative effects in humans. However, a possibility to utilize PFOA/PFOS-like substances for activating UCP1 therapeutically in obesity-prone humans may also be envisaged.
Labels: MiParea: mt-Membrane, Comparative MiP;environmental MiP, Pharmacology;toxicology
Organism: Mouse Tissue;cell: Fat Preparation: Isolated mitochondria
Event: E1 MiP2015
Dept Mol Biosc, Wenner-Gren Inst, Stockholm Univ, Sweden. - [email protected]
References and acknowledgements
- Shabalina IG, Kramarova TV, Mattsson CL, Petrovic N, Qazi Rahman M, Csikasz RI, Chang S-C, Butenhoff J, DePierre JW, Cannon B, Nedergaard J (2015). The environmental pollutants perfluorooctane sulfonate and perfluorooctanoic acid upregulate uncoupling protein 1 (UCP1) in brown-fat mitochondria through a UCP1-dependent reduction in food intake. Toxicological Sc 46:334-43.