Xenon‐enhanced computed tomography assessment of brown adipose tissue distribution and perfusion in lean, obese, and diabetic primates

Garside, John; Kavanagh, Kylie; Block, Masha; Williams, Abigail G.; Branca, Rosa T.

doi:10.1002/oby.23519

Cited by 7 publications

(5 citation statements)

References 44 publications

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“…Imaging experiments confirmed that this resonance originated primarily from 129 Xe spins located within the supraclavicular fat depot, where BAT is known to be present in humans. Overall, these results mimic the results previously obtained in rodents and non-human primates, which have shown a selective increase in xenon uptake in the brown fat of anesthetized mice and non-human primates during stimulation of thermogenesis by catecholamines 34 , 38 , 42 . In humans, the absence of a strong lipid peak before stimulation of thermogenesis confirms that at thermoneutrality BAT is not very well perfused, leading to reduced wash-in rate and low uptake of polarized 129 Xe atoms in the tissue.…”

Section: Discussionsupporting

confidence: 89%

“…While the solubility of xenon in fat is twenty fold higher than in any other tissue compartment 32 , 33 , low blood perfusion generally limits the concentration of xenon reached in fat after a single inhalation of the gas 34 . On the other hand, detectable concentrations of xenon are expected to be found in highly perfused fat tissues like brown fat, especially during stimulation of thermogenesis, when tissue blood flow increases 35 – 38 . Finally, the LDX chemical shift is very sensitive to the temperature-induced changes in the density of fat 39 , 40 .…”

Section: Introductionmentioning

confidence: 99%

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Absolute thermometry of human brown adipose tissue by magnetic resonance with laser polarized 129Xe

Zhang,

Antonacci,

Burant

et al. 2023

Commun Med

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Background Absolute temperature measurements of tissues inside the human body are difficult to perform non-invasively. Yet, for brown adipose tissue (BAT), these measurements would enable direct monitoring of its thermogenic activity and its association with metabolic health. Methods Here, we report direct measurement of absolute BAT temperature in humans during cold exposure by magnetic resonance (MR) with laser polarized xenon gas. This methodology, which leverages on the sensitivity of the chemical shift of the 129Xe isotope to temperature-induced changes in fat density, is first calibrated in vitro and then tested in vivo in rodents. Finally, it is used in humans along with positron emission tomography (PET) scans with fluorine-18-fluorodeoxyglucose to detect BAT thermogenic activity during cold exposure. Results Absolute temperature measurements, obtained in rodents with an experimental error of 0.5 °C, show only a median deviation of 0.12 °C against temperature measurements made using a pre-calibrated optical temperature probe. In humans, enhanced uptake of 129Xe in BAT during cold exposure leads to background-free detection of this tissue by MR. Global measurements of supraclavicular BAT temperature, made over the course of four seconds and with an experimental error ranging from a minimum of 0.4 °C to more than 2 °C, in case of poor shimming, reveal an average BAT temperature of 38.8° ± 0.8 °C, significantly higher (p < 0.02 two-sided t test) than 37.7 °C. Hot BAT is also detected in participants with a PET scan negative for BAT. Conclusions Non-invasive, radiation-free measurements of BAT temperature by MRI with hyperpolarized 129Xe may enable longitudinal monitoring of human BAT activity under various stimulatory conditions.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Absolute thermometry of human brown adipose tissue by magnetic resonance with laser polarized 129Xe

Zhang,

Antonacci,

Burant

et al. 2023

Commun Med

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“…Oelkrug et al, 2015; Soppela et al, 1992) and non‐human primates (e.g. Garside et al, 2022; Williams et al, 2023).…”

Section: Resting Metabolic Rate Total Energy Expenditure (Tee) and Br...mentioning

confidence: 99%

Human cold adaptation: An unfinished agenda v2.0

Ocobock

2023

American J Hum Biol

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BackgroundResearch on human extreme cold climate adaptations has benefitted from a recent resurgence since Ted Steegmann laid out his Human Cold Adaptation Agenda in 2007. Human biologists have drastically expanded our knowledge in this area during the last 15 years, but we still have a great deal more work to do to fulfill the cold climate adaptation agenda.MethodsHere, I follow Steegmann's example by providing a review of cold climate adaptations and setting forth a new, expanded agenda.ResultsI review the foundational work on cold climate adaptations including classic Bergmann, Allen, and Thomson rules as well as early work assessing metabolic differences among Indigenous cold climate populations. From there, I discuss some of the groundbreaking work currently taking place on cold climate adaptations such as brown adipose tissue (a heat generating organ), physical activity levels, metabolic rates, and behavioral/cultural mechanisms. Finally, I present a path forward for future research with a focus on some of the basic extreme cold adaptations as well as how human biologists should approach the effects of climate change on human health and well‐being, particularly within a cold climate context.ConclusionThe Arctic has felt the dramatic effects of climate change sooner and more acutely than other parts of the world, making it an ideal location for studying both cold climate adaptations and climate change resilience. Human biologists have a great deal to contribute to the conversation on not only adaptations to extreme cold, but also the ways in which climate change is being embodied by cold climate populations.

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“…This was demonstrated not only in lean mice, which present a very hydrated and perfused BAT, but also in obese mice in which the main interscapular BAT morphologically resembles beige fat. More recently, this technique was used to detect small clusters of BAT located within the supraclavicular, axillary, and perirenal regions of lean non-human primates and non-human primates with obesity 27 .…”

Section: Introductionmentioning

confidence: 99%

In-vivo detection of white adipose tissue browning: a multimodality imaging approach

Holmes,

Garside,

Frank

et al. 2023

Sci Rep

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Detection and differentiation of brown fat in humans poses several challenges, as this tissue is sparse and often mixed with white adipose tissue. Non-invasive detection of beige fat represents an even greater challenge as this tissue is structurally and functionally more like white fat than brown fat. Here we used positron emission tomography with 18F-fluorodeoxyglucose, computed tomography, xenon-enhanced computed tomography, and dynamic contrast-enhanced ultrasound, to non-invasively detect functional and structural changes associated with the browning process of inguinal white fat, induced in mice by chronic stimulation with the β3-adrenergic receptor agonist CL-316243. These studies reveal a very heterogeneous increase in baseline tissue radiodensity and xenon-enhanced radiodensity, indicative of both an increase in adipocytes water and protein content as well as tissue perfusion, mostly in regions that showed enhanced norepinephrine-stimulated perfusion before CL-316243 treatment. No statistically significant increase in 18F-fluorodeoxyglucose uptake or norepinephrine-stimulated tissue perfusion were observed in the mice after the CL-316243 treatment. The increase in tissue-water content and perfusion, along with the negligible increase in the tissue glucose uptake and norepinephrine-stimulated perfusion deserve more attention, especially considering the potential metabolic role that this tissue may play in whole body metabolism.

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Xenon‐enhanced computed tomography assessment of brown adipose tissue distribution and perfusion in lean, obese, and diabetic primates

Cited by 7 publications

References 44 publications

Absolute thermometry of human brown adipose tissue by magnetic resonance with laser polarized 129Xe

Absolute thermometry of human brown adipose tissue by magnetic resonance with laser polarized 129Xe

Human cold adaptation: An unfinished agenda v2.0

In-vivo detection of white adipose tissue browning: a multimodality imaging approach

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