title: Within brown-fat cells, UCP1-mediated fatty acid-induced uncoupling is independent of fatty acid metabolism.
abstract: In the present investigation, we have utilized the availability of UCP1(-/-) mice to examine a wide range of previously proposed lipid activators of Uncoupling Protein 1 (UCP1) in its native environment, i.e. in the brown-fat cells. A non-metabolizable fatty acid analogue, beta,beta cent-methyl-substituted hexadecane alpha,omega-dicarboxylic acid (Medica-16) is a potent UCP1 (re)activator in brown-fat cells, despite its bipolar structure. All-trans-retinoic acid activates UCP1 within cells, whereas beta-carotene only does so after metabolism. The UCP1-dependent effects of fatty acids are positively correlated with their chain length. Medium-chain fatty acids are potent UCP1 activators in cells, despite their lack of protonophoric properties in mitochondrial membranes. Thus, neither the ability to be metabolized nor an innate uncoupling/protonophoric ability is a necessary property of UCP1 activators within brown-fat cells.
authors.affiliation: The Wenner-Gren Institute, The Arrhenius Laboratories F3, Stockholm University, SE-106 91 Stockholm, Sweden.
authors.forename: Irina G
authors.initials: IG
authors.lastname: Shabalina
authors.forename: Emma C
authors.initials: EC
authors.lastname: Backlund
authors.forename: Jacob
authors.initials: J
authors.lastname: Bar-Tana
authors.forename: Barbara
authors.initials: B
authors.lastname: Cannon
authors.forename: Jan
authors.initials: J
authors.lastname: Nedergaard
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D005227:Fatty Acids / Q000378:metabolism* / Q000494:pharmacology; D006153:Guanosine Diphosphate / Q000378:metabolism; D007473:Ion Channels / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D000071256:Uncoupling Protein 1
chemical_list: D005227:Fatty Acids; D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D006153:Guanosine Diphosphate; D000255:Adenosine Triphosphate