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In vivo noninvasive characterization of brown adipose tissue blood flow by contrast ultrasound in mice

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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. Methods and 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 mu g.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.
Keywords
imaging, contrast ultrasound, brown adipose tissue, uncoupling protein, nitric oxide synthase, DIET-INDUCED THERMOGENESIS, NITRIC-OXIDE SYNTHASE, ADULT HUMANS, NONSHIVERING THERMOGENESIS, MYOCARDIAL-PERFUSION, OXYGEN-CONSUMPTION, COLD-EXPOSURE, WILD-TYPE, RAT, NORADRENALINE

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Citation

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Chicago
Baron, David M, Maeva Clerte, Peter Brouckaert, Michael J Raher, Aidan W Flynn, Haihua Zhang, Edward A Carter, et al. 2012. “In Vivo Noninvasive Characterization of Brown Adipose Tissue Blood Flow by Contrast Ultrasound in Mice.” Circulation-cardiovascular Imaging 5 (5): 652–659.
APA
Baron, D. M., Clerte, M., Brouckaert, P., Raher, M. J., Flynn, A. W., Zhang, H., Carter, E. A., et al. (2012). In vivo noninvasive characterization of brown adipose tissue blood flow by contrast ultrasound in mice. CIRCULATION-CARDIOVASCULAR IMAGING, 5(5), 652–659.
Vancouver
1.
Baron DM, Clerte M, Brouckaert P, Raher MJ, Flynn AW, Zhang H, et al. In vivo noninvasive characterization of brown adipose tissue blood flow by contrast ultrasound in mice. CIRCULATION-CARDIOVASCULAR IMAGING. 2012;5(5):652–9.
MLA
Baron, David M, Maeva Clerte, Peter Brouckaert, et al. “In Vivo Noninvasive Characterization of Brown Adipose Tissue Blood Flow by Contrast Ultrasound in Mice.” CIRCULATION-CARDIOVASCULAR IMAGING 5.5 (2012): 652–659. Print.
@article{3131002,
  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. 
Methods and 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 mu g.kg(-1).min(-1)). Assessment of BAT blood flow using CU was correlated to that performed with fluorescent microspheres (R-2=0.86, P{\textlangle}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.},
  author       = {Baron, David M and Clerte, Maeva and Brouckaert, Peter and Raher, Michael J and Flynn, Aidan W and Zhang, Haihua and Carter, Edward A and Picard, Michael H and Bloch, Kenneth D and Buys, Emmanuel S and Scherrer-Crosbie, Marielle},
  issn         = {1941-9651},
  journal      = {CIRCULATION-CARDIOVASCULAR IMAGING},
  keyword      = {imaging,contrast ultrasound,brown adipose tissue,uncoupling protein,nitric oxide synthase,DIET-INDUCED THERMOGENESIS,NITRIC-OXIDE SYNTHASE,ADULT HUMANS,NONSHIVERING THERMOGENESIS,MYOCARDIAL-PERFUSION,OXYGEN-CONSUMPTION,COLD-EXPOSURE,WILD-TYPE,RAT,NORADRENALINE},
  language     = {eng},
  number       = {5},
  pages        = {652--659},
  title        = {In vivo noninvasive characterization of brown adipose tissue blood flow by contrast ultrasound in mice},
  url          = {http://dx.doi.org/10.1161/CIRCIMAGING.112.975607},
  volume       = {5},
  year         = {2012},
}

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