title: Brown adipose tissue dynamics in wild-type and UCP1-knockout mice: in vivo insights with magnetic resonance.
abstract: We used noninvasive magnetic resonance imaging (MRI) and magnetic resonance spectroscopy to compare interscapular brown adipose tissue (iBAT) of wild-type (WT) and uncoupling protein 1 (UCP1)-knockout mice lacking UCP1-mediated nonshivering thermogenesis (NST). Mice were sequentially acclimated to an ambient temperature of 30°C, 18°C, and 5°C. We detected a remodeling of iBAT and a decrease in its lipid content in all mice during cold exposure. Ratios of energy-rich phosphates (ATP/ADP, phosphocreatine/ATP) in iBAT were maintained stable during noradrenergic stimulation of thermogenesis in cold- and warm-adapted mice and no difference between the genotypes was observed. As free fatty acids (FFAs) serve as fuel for thermogenesis and activate UCP1 for uncoupling of oxidative phosphorylation, brown adipose tissue is considered to be a main acceptor and consumer of FFAs. We measured a major loss of FFAs from iBAT during noradrenergic stimulation of thermogenesis. This mobilization of FFAs was observed in iBAT of WT mice as well as in mice lacking UCP1. The high turnover and the release of FFAs from iBAT suggests an enhancement of lipid metabolism, which in itself contributes to the sympathetically activated NST and which is independent from uncoupled respiration mediated by UCP1. Our study demonstrates that MRI, besides its potential for visualizing and quantification of fat tissue, is a valuable tool for monitoring functional in vivo processes like lipid and phosphate metabolism during NST.
authors.affiliation: Faculty of Biology, Department of Animal Physiology, Philipps-Universität Marburg, 35043 Marburg, Germany.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Grimpo
authors.forename: Maximilian N
authors.initials: MN
authors.lastname: Völker
authors.forename: Eva N
authors.initials: EN
authors.lastname: Heppe
authors.forename: Steve
authors.initials: S
authors.lastname: Braun
authors.forename: Johannes T
authors.initials: JT
authors.lastname: Heverhagen
authors.forename: Gerhard
authors.initials: G
authors.lastname: Heldmaier
mesh_terms: D000064:Acclimatization / Q000235:genetics / Q000502:physiology; D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D003080:Cold Temperature; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D051379:Mice; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D010085:Oxidative Phosphorylation; D010101:Oxygen Consumption; D010725:Phosphocreatine / Q000378:metabolism; D022722:Thermogenesis / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D000071256:Uncoupling Protein 1
chemical_list: D005230:Fatty Acids, Nonesterified; D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D010725:Phosphocreatine; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D009638:Norepinephrine
keywords: lipid metabolism; nonshivering thermogenesis; phosphorus spectroscopy; proton spectroscopy; ultra-high field; uncoupling protein 1