title: In vivo noninvasive characterization of brown adipose tissue blood flow by contrast ultrasound in mice.
abstract: BACKGROUND
  Interventions to increase brown adipose tissue (BAT) volume and activation are being extensively investigated as therapies to decrease the body weight in obese subjects. Noninvasive methods to monitor these therapies in animal models and humans are rare. We investigated whether contrast ultrasound (CU) performed in mice could detect BAT and measure its activation by monitoring BAT blood flow. After validation, CU was used to study the role of uncoupling protein 1 and nitric oxide synthases in the acute regulation of BAT blood flow.
  
  
  RESULTS
  Blood flow of interscapular BAT was assessed in mice (n=64) with CU by measuring the signal intensity of continuously infused contrast microbubbles. Blood flow of BAT estimated by CU was 0.5±0.1 (mean±SEM) dB/s at baseline and increased 15-fold during BAT stimulation by norepinephrine (1 µg·kg(-1)·min(-1)). Assessment of BAT blood flow using CU was correlated to that performed with fluorescent microspheres (R(2)=0.86, P<0.001). To evaluate whether intact BAT activation is required to increase BAT blood flow, CU was performed in uncoupling protein 1-deficient mice with impaired BAT activation. Norepinephrine infusion induced a smaller increase in BAT blood flow in uncoupling protein 1-deficient mice than in wild-type mice. Finally, we investigated whether nitric oxide synthases played a role in acute norepinephrine-induced changes of BAT blood flow. Genetic and pharmacologic inhibition of nitric oxide synthase 3 attenuated the norepinephrine-induced increase in BAT blood flow.
  
  
  CONCLUSIONS
  These results indicate that CU can detect BAT in mice and estimate BAT blood flow in mice with functional differences in BAT.
authors: Anesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors: David M
authors: DM
authors: Baron
authors: Maeva
authors: M
authors: Clerte
authors: Peter
authors: P
authors: Brouckaert
authors: Michael J
authors: MJ
authors: Raher
authors: Aidan W
authors: AW
authors: Flynn
authors: Haihua
authors: H
authors: Zhang
authors: Edward A
authors: EA
authors: Carter
authors: Michael H
authors: MH
authors: Picard
authors: Kenneth D
authors: KD
authors: Bloch
authors: Emmanuel S
authors: ES
authors: Buys
authors: Marielle
authors: M
authors: Scherrer-Crosbie
mesh_terms: D002001:Adipose Tissue, Brown / Q000098:blood supply* / Q000378:metabolism; D000818:Animals; D001783:Blood Flow Velocity; D002302:Cardiac Output; D003287:Contrast Media / Q000008:administration & dosage; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005240:Feasibility Studies; D005456:Fluorescent Dyes; D005466:Fluorocarbons / Q000008:administration & dosage; D005786:Gene Expression Regulation; D006439:Hemodynamics / Q000187:drug effects; D007262:Infusions, Intravenous; D007473:Ion Channels / Q000172:deficiency / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D045423:Microbubbles; D024101:Mitochondrial Proteins / Q000172:deficiency / Q000235:genetics; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics; D009638:Norepinephrine / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012039:Regional Blood Flow; D013997:Time Factors; D000071256:Uncoupling Protein 1
chemical_list: D003287:Contrast Media; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D005466:Fluorocarbons; D007473:Ion Channels; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; C000604371:UCP1 protein, human; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; C042852:perflutren; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D009638:Norepinephrine