Abstract
The metabolically inert perfluorinated fatty acids perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) can display fatty acid-like activity in biological systems. The uncoupling protein 1 (UCP1) in brown adipose tissue is physiologically (re)activated by fatty acids, including octanoate. This leads to bioenergetically uncoupled energy dissipation (heat production, thermogenesis). We have examined here the possibility that PFOA/PFOS can directly (re)activate UCP1 in isolated mouse brown-fat mitochondria. In wild-type 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. No effect was observed in heart mitochondria, i.e., in mitochondria without UCP1. The stimulatory effect of PFOA/PFOS was not secondary to non-specific mitochondrial membrane permeabilization 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.Electronic supplementary materialThe online version of this article (doi:10.1007/s00204-015-1535-4) contains supplementary material, which is available to authorized users.
Highlights
Perfluorinated compounds have been utilized in a wide variety of commercial products, due to their unique surface active properties, the stability of their C–F bonds, and their thermal resistivity
In order to examine whether the fatty acid-like perfluorinated compounds PFOA and perfluorooctane sulfonate (PFOS) could interact with uncoupling protein 1 (UCP1)-mediated thermogenic processes in brown-fat mitochondria, we isolated brown-fat mitochondria from wild-type and UCP1 KO mice
We demonstrate a very specific ability of the perfluorinated fatty acids PFOA and PFOS to induce oxygen consumption in brown-fat mitochondria through activation of UCP1
Summary
Perfluorinated compounds have been utilized in a wide variety of commercial products, due to their unique surface active properties, the stability of their C–F bonds, and their thermal resistivity. These products include grease-resistant food wrapping, firefighting foams, and ski wax. Due to their stability, perfluorinated compounds accumulate in nature, and the presence of perfluorinated compounds in the environment and in bodily fluids of humans and wildlife has been well documented (Beesoon et al 2012; Kannan et al 2006; Theobald et al 2011; Zhang et al 2013). Being structurally similar to a fatty acid, the possibility may be raised that PFOA and PFOS exhibit
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