Metabolically inert perfluorinated fatty acids directly activate uncoupling protein 1 in brown-fat mitochondria. 2016

Irina G Shabalina, and Anastasia V Kalinovich, and Barbara Cannon, and Jan Nedergaard
Department of Molecular Biosciences, The Wenner-Gren Institute, The Arrhenius Laboratories F3, Stockholm University, SE-106 91, Stockholm, Sweden.

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.

UI MeSH Term Description Entries
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D008928 Mitochondria Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed) Mitochondrial Contraction,Mitochondrion,Contraction, Mitochondrial,Contractions, Mitochondrial,Mitochondrial Contractions
D008929 Mitochondria, Heart The mitochondria of the myocardium. Heart Mitochondria,Myocardial Mitochondria,Mitochondrion, Heart,Heart Mitochondrion,Mitochondria, Myocardial
D008933 Mitochondrial Swelling An increase in MITOCHONDRIAL VOLUME due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. Giant Mitochondria,Megamitochondria,Mitochondrial Hypertrophy,Giant Mitochondrias,Hypertrophy, Mitochondrial,Megamitochondrias,Mitochondria, Giant,Mitochondrial Hypertrophies,Swelling, Mitochondrial
D010101 Oxygen Consumption The rate at which oxygen is used by a tissue; microliters of oxygen STPD used per milligram of tissue per hour; the rate at which oxygen enters the blood from alveolar gas, equal in the steady state to the consumption of oxygen by tissue metabolism throughout the body. (Stedman, 25th ed, p346) Consumption, Oxygen,Consumptions, Oxygen,Oxygen Consumptions
D002001 Adipose Tissue, Brown A thermogenic form of adipose tissue composed of BROWN ADIPOCYTES. It is found in newborns of many species including humans, and in hibernating mammals. Brown fat is richly vascularized, innervated, and densely packed with MITOCHONDRIA which can generate heat directly from the stored lipids. Brown Fat,Hibernating Gland,Brown Adipose Tissue,Fat, Brown,Tissue, Brown Adipose
D002210 Caprylates Derivatives of caprylic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain a carboxy terminated eight carbon aliphatic structure. Caprylate,Octanoates,Caprylic Acids,Octanoic Acids,Acids, Caprylic,Acids, Octanoic
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004734 Energy Metabolism The chemical reactions involved in the production and utilization of various forms of energy in cells. Bioenergetics,Energy Expenditure,Bioenergetic,Energy Expenditures,Energy Metabolisms,Expenditure, Energy,Expenditures, Energy,Metabolism, Energy,Metabolisms, Energy
D005466 Fluorocarbons Liquid perfluorinated carbon compounds which may or may not contain a hetero atom such as nitrogen, oxygen or sulfur, but do not contain another halogen or hydrogen atom. This concept includes fluorocarbon emulsions, and fluorocarbon blood substitutes. Perfluorinated and related polyfluorinated chemicals are referred to as PFAS and are defined as chemicals with at least two adjacent carbon atoms, where one carbon is fully fluorinated and the other is at least partially fluorinated. Fluorocarbon,Fluorocarbon Emulsion,Fluorocarbon Emulsions,Fluorotelomer Phosphate Esters,N-Alkyl Perfluoroalkyl Sulfonamido Carboxylates,PFAS Per- and Polyfluoroalkyl Substances,PFC Perfluorinated Chemicals,PFECAs Perfluoropolyether Carboxylic Acids,Per- and Polyfluoroalkyl Substances,Perfluoroalkane Sulfonamides,Perfluoroalkyl Carboxylates,Perfluoroalkyl Ether Carboxylates,Perfluoroalkyl Polyether Carboxylates,Perfluorocarbon,Perfluorocarbons,Perfluoropolyether Carboxylic Acids,Polyfluorocarbons,Fluorinated Telomer Alcohols,Fluoro-Telomer Alcohols,Polyfluorinated Telomer Alcohols,Telomer Fluorocarbons,Acids, Perfluoropolyether Carboxylic,Alcohols, Fluorinated Telomer,Alcohols, Fluoro-Telomer,Alcohols, Polyfluorinated Telomer,Carboxylates, Perfluoroalkyl,Carboxylates, Perfluoroalkyl Ether,Carboxylates, Perfluoroalkyl Polyether,Carboxylic Acids, Perfluoropolyether,Chemicals, PFC Perfluorinated,Emulsion, Fluorocarbon,Emulsions, Fluorocarbon,Esters, Fluorotelomer Phosphate,Ether Carboxylates, Perfluoroalkyl,Fluoro Telomer Alcohols,Fluorocarbons, Telomer,N Alkyl Perfluoroalkyl Sulfonamido Carboxylates,PFAS Per and Polyfluoroalkyl Substances,Per and Polyfluoroalkyl Substances,Perfluorinated Chemicals, PFC,Phosphate Esters, Fluorotelomer,Polyether Carboxylates, Perfluoroalkyl,Sulfonamides, Perfluoroalkane,Telomer Alcohols, Fluorinated,Telomer Alcohols, Polyfluorinated

Related Publications

Irina G Shabalina, and Anastasia V Kalinovich, and Barbara Cannon, and Jan Nedergaard
August 1985, Journal of biochemistry,
Irina G Shabalina, and Anastasia V Kalinovich, and Barbara Cannon, and Jan Nedergaard
April 2003, Archives of biochemistry and biophysics,
Irina G Shabalina, and Anastasia V Kalinovich, and Barbara Cannon, and Jan Nedergaard
October 2012, Cell,
Irina G Shabalina, and Anastasia V Kalinovich, and Barbara Cannon, and Jan Nedergaard
June 1984, Biochemical Society transactions,
Irina G Shabalina, and Anastasia V Kalinovich, and Barbara Cannon, and Jan Nedergaard
October 2023, Life sciences,
Irina G Shabalina, and Anastasia V Kalinovich, and Barbara Cannon, and Jan Nedergaard
May 1996, Biological & pharmaceutical bulletin,
Irina G Shabalina, and Anastasia V Kalinovich, and Barbara Cannon, and Jan Nedergaard
January 1986, Methods in enzymology,
Irina G Shabalina, and Anastasia V Kalinovich, and Barbara Cannon, and Jan Nedergaard
September 2018, The British journal of nutrition,
Irina G Shabalina, and Anastasia V Kalinovich, and Barbara Cannon, and Jan Nedergaard
January 2006, The international journal of biochemistry & cell biology,
Irina G Shabalina, and Anastasia V Kalinovich, and Barbara Cannon, and Jan Nedergaard
October 1969, Hoppe-Seyler's Zeitschrift fur physiologische Chemie,
Copied contents to your clipboard!