Dataset Information

MRI Reveals Human Brown Adipose Tissue Is Rapidly Activated in Response to Cold.

ABSTRACT: Context:In rodents, cold exposure induces the activation of brown adipose tissue (BAT) and the induction of intracellular triacylglycerol (TAG) lipolysis. However, in humans, the kinetics of supraclavicular (SCV) BAT activation and the potential importance of TAG stores remain poorly defined. Objective:To determine the time course of BAT activation and changes in intracellular TAG using MRI assessment of the SCV (i.e., BAT depot) and fat in the posterior neck region (i.e., non-BAT). Design:Cross-sectional. Setting:Clinical research center. Patients or Other Participants:Twelve healthy male volunteers aged 18 to 29 years [body mass index = 24.7 ± 2.8 kg/m2 and body fat percentage = 25.0% ± 7.4% (both, mean ± SD)]. Interventions:Standardized whole-body cold exposure (180 minutes at 18°C) and immediate rewarming (30 minutes at 32°C). Main Outcome Measures:Proton density fat fraction (PDFF) and T2* of the SCV and posterior neck fat pads. Acquisitions occurred at 5- to 15-minute intervals during cooling and subsequent warming. Results:SCV PDFF declined significantly after only 10 minutes of cold exposure [-1.6% (SE: 0.44%; P = 0.007)] and continued to decline until 35 minutes, after which time it remained stable until 180 minutes. A similar time course was also observed for SCV T2*. In the posterior neck fat (non-BAT), there were no cold-induced changes in PDFF or T2*. Rewarming did not result in a change in SCV PDFF or T2*. Conclusions:The rapid cold-induced decline in SCV PDFF suggests that in humans BAT is activated quickly in response to cold and that TAG is a primary substrate.

SUBMITTER: Oreskovich SM

PROVIDER: S-EPMC6855213 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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MRI Reveals Human Brown Adipose Tissue Is Rapidly Activated in Response to Cold.

Oreskovich Stephan M SM Ong Frank J FJ Ahmed Basma A BA Konyer Norman B NB Blondin Denis P DP Gunn Elizabeth E Singh Nina P NP Noseworthy Michael D MD Haman Francois F Carpentier Andre C AC Punthakee Zubin Z Steinberg Gregory R GR Morrison Katherine M KM

Journal of the Endocrine Society 20191014 12

<h4>Context</h4>In rodents, cold exposure induces the activation of brown adipose tissue (BAT) and the induction of intracellular triacylglycerol (TAG) lipolysis. However, in humans, the kinetics of supraclavicular (SCV) BAT activation and the potential importance of TAG stores remain poorly defined.<h4>Objective</h4>To determine the time course of BAT activation and changes in intracellular TAG using MRI assessment of the SCV (<i>i.e.,</i> BAT depot) and fat in the posterior neck region (<i>i.e ...[more]

PMID: 31745532

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Project description:UnlabelledIn animals, defective brown adipogenesis leads to bone loss. Whether brown adipose tissue (BAT) mass relates to bone mineral density (BMD) in humans is unclear. We determined the relationship between BAT mass and BMD by cold-stimulated positron-emission tomography (PET) and dual-energy X-ray absorptiometry (DXA) in healthy volunteers. Higher BAT mass was associated with higher BMD in healthy women, but not in men, independent of age and body composition.IntroductionContrary to the traditional belief that BAT is present only in infants, recent studies revealed significant depots of BAT present in adult humans. In animals, defective brown adipogenesis leads to bone loss. While white adipose tissue mass is a known determinant of BMD in humans, the relationship between BAT and BMD in humans is unclear. We thus examined the relationship between BAT and BMD in healthy adults.MethodsBAT volume (ml) and activity (standard uptake value) were determined by 18F-fluorodeoxyglucose PET after overnight mild cold exposure at 19 °C, and BMD was determined by DXA.ResultsAmong 24 healthy adults (age 28±1 years, F=10), BAT volumes were 82.4±99.5 ml in women and 49.7±54.5 ml in men. Women manifested significantly higher BAT activity, by 9.4±8.1% (p=0.03), than men. BAT volume correlated positively with total and spine BMD (r2=0.40 and 0.49, respectively, p<0.02) in women and remained a significant predictor after adjustment for age, fat, and lean body mass (p<0.05). Total and spine BMD were higher in women who harbored visually detectable BAT on PET images than those without by 11±2% (p=0.02) and 22±2% (p<0.01), respectively. No associations were observed between BAT parameters and BMD in men.ConclusionsThis study demonstrated higher BMD among healthy women with more abundant BAT, independent of age and other body compositional parameters. This was not observed in men. The data suggest that brown adipogenesis may be physiologically related to modulation of bone density.

Project description:Regulation of the thermogenic response by brown adipose tissue (BAT) is an important mechanism in the basic biology and treatment of obesity and diabetes. Consensus transcriptional regulatory analysis of a publicly-available RNA-seq dataset uncovered a large number of nodes representing epigenetic modifiers that were altered in BAT in response to chronic thermogenic activation. Thus, we hypothesized that chronic activation of BAT results in epigenetic modifications of DNA and histones that affect the tissue function. To test our hypothesis, wildtype male C57BL/6J mice were housed under chronic conditions of thermoneutral temperature (TN, 28.8°C), mild cold/room temperature (RT, 22°C), or severe cold (SC, 8°C). Reduced representation bisulfite sequencing (RRBS) revealed a marked decrease in methylation of promoters and intragenic regions in BAT genomic DNA in response to varying degrees of chronic cold exposure. Integration of our RRBS and the publicly available RNA-Seq dataset suggested a role for epigenetic modification of DNA in gene regulation in response to cold. To analyze histone modifications, we developed a robust method for the isolation and quantitation of histone proteoforms, which enabled the first comparison of histone H3.2 and H4 proteoforms in BAT. We report distinct on/off histone signals that are observed with histone H3.2 in BAT, but not in the liver, when mice are acclimated to severe cold in comparison with mild cold. Specifically, we observe a larger percentage of histone H3.2 with the K9 dimethylation mark coupled with K36 mono- or di-methylation and K23 acetylation, suggesting strong repression of previously active chromatin. Taken together, our results provide novel findings supporting global epigenetic modification in murine BAT in response to varying degrees of chronic cold stimuli and establish a methodology to quantitatively study histones in BAT, allowing for direct comparisons to decipher mechanistic changes during the thermogenic response.

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MRI Reveals Human Brown Adipose Tissue Is Rapidly Activated in Response to Cold.

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MRI Reveals Human Brown Adipose Tissue Is Rapidly Activated in Response to Cold.

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