Correlation of Brown Adipose Tissue with Other Body Fat Compartments and Patient Characteristics

Brendle, Cornelia; Werner, Matthias; Schmadl, Maria; Fougère, Christian la; Nikolaou, Konstantin; Stefan, Norbert; Pfannenberg, Christina

doi:10.1016/j.acra.2017.09.007

Cited by 63 publications

(63 citation statements)

References 44 publications

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“…The finding that beside the interaction term, BMI and age are drivers of supraclavicular PDFF with lower BMI and younger age leading to lower supraclavicular PDFF, thus presumably more BAT, is consistent with results from PET/CT studies showing lower BMI and younger age being associated with more (activated) BAT [49,[58][59][60].…”

Section: Discussionsupporting

confidence: 83%

“…One strength of the present analysis is the relatively high number of volunteers included, compared to other studies that are mostly based on PET imaging with smaller patient numbers or with a retrospective design [15,17,53,59]. Secondly, imaging of BAT based on PET data relies on the current metabolic activity of the tissue, while MRI provides a more robust parameter -the PDFF -for differentiating BAT from WAT, independent from the metabolic status.…”

Section: Strengths and Limitationsmentioning

confidence: 99%

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Investigation of the Relationship between MR-Based Supraclavicular Fat Fraction and Thyroid Hormones

et al. 2020

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Purpose: Brown adipose tissue (BAT) plays a potential role in energy and glucose metabolism in humans. Thyroid hormones (TH) are main regulators of BAT development and function. However, it remains unknown how the magnetic resonance (MR)-based proton density fat fraction (PDFF) of supraclavicular adipose tissue used as a surrogate marker for BAT presence relates to TH. Therefore, the purpose of this analysis was to investigate the relationship between supraclavicular PDFF and serum levels of TH. Methods: In total, 96 adult volunteers from a large cross-sectional study who underwent additional MR examination of the neck and pelvis were included in this analysis. Segmented PDFF maps of the supraclavicular and gluteal subcutaneous adipose tissue were generated. Delta PDFF was calculated as the difference between gluteal and supraclavicular PDFF and grouped as high (≥12%) or low (<12%) based on the median and the clinical rationale of a high versus low probability of BAT being present. Thyroid-stimulating hormone (mIU/L), free triiodothyronine (FT3, pg/mL) and free thyroxine (FT4, ng/dL) levels were determined in blood samples. Body mass index (BMI) was calculated as weight (kg)/height (m)². Statistical analyses included the use of paired samples ttest, simple linear regression analysis and a multivariable linear regression analysis. Results: The median age of the subjects (77% female) was 33 years, BMI ranged from 17.2 to 43.1 kg/m². Supraclavicular and gluteal PDFF differed significantly (76.5 ± 4.8 vs. 89.4 ± 3.5 %, p < 0.01). Supraclavicular PDFF was associated with FT3 in subjects with high delta PDFF (R² = 0.17, p < 0.01), with higher FT3 being associated with lower supraclavicular PDFF (y = 85.2 + –3.6 x). In a multivariable linear regression analysis considering further potential prognostic factors, the interaction between the delta PDFF group and FT3 remained a predictor for supraclavicular PDFF (B = –4.65, p < 0.01). Discussion/Conclusions: Supraclavicular PDFF corresponds to the presence of BAT. In the present analysis, supraclavicular PDFF is correlated with FT3 in subjects with high delta PDFF. Therefore, the present findings suggest that biologically active T3 may be involved in the development of supraclavicular BAT.

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Section: Discussionsupporting

confidence: 83%

Section: Strengths and Limitationsmentioning

confidence: 99%

Investigation of the Relationship between MR-Based Supraclavicular Fat Fraction and Thyroid Hormones

et al. 2020

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“…Obese humans have reduced BAT compared to those with normal weight [31]. A recent study employing retrospective analysis of FDG-PET/CT scans of 4852 patients showed that BAT-positive patients had lower visceral, subcutaneous and liver fat content [32]. In this study, although body weight did not differ significantly between SCD-fed ASKO and WT mice, ASKO mice were more susceptible to HFD-induced obesity.…”

Section: Discussioncontrasting

confidence: 55%

Adaptor protein APPL1 coordinates HDAC3 to modulate brown adipose tissue thermogenesis in mice

Fan

Wan

et al. 2019

Metabolism

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Objectives: The activation of brown adipose tissue (BAT) is considered as a promising therapeutic target for obesity. APPL1 (Adaptor protein containing the Pleckstrin homology domain, Phosphotyrosine binding domain and Leucine zipper motif) is an intracellular adaptor protein and its genetic variation is correlated with BMI and body fat distribution in diabetic patients. However, little is known about the roles of APPL1 in BAT thermogenesis. Materials/methods: In this study, adipose tissue specific knockout (ASKO) mice were generated to evaluate APPL1's role in BAT thermogenesis in vivo, and possible signaling pathways were further explored in cultured brown adipocytes. Results: After high fat diet challenge, APPL1 ASKO mice developed more severe obesity, glucose intolerance and insulin resistance compared with control mice. Metabolic cage study showed that APPL1 deficiency impaired energy expenditure and adaptive thermogenesis in ASKO mice. PET-CT analysis showed decreased standardized uptake value (SUV) in the inter-scapular region which indicated impaired BAT activity in ASKO mice. Further study showed deletion of APPL1 attenuated brown fat specific gene expression, such as UCP1 and PGC1α in both BAT and brown adipocytes. In cultured brown adipocytes, upon cAMP stimulation, APPL1 shuttled from cytosol to nuclei. Co-IP and ChIP study showed that APPL1 could directly interact with histone deacetylase 3 (HDAC3) to mediate chromatin remodeling and UCP1 gene expression. Conclusions: Our data demonstrated the essential role of APPL1 in regulating brown adipocytes thermogenesis via interaction with HDAC3, which may have potential therapeutic implications for treatment of obesity.

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“…A recent study using elegant tracer studies in humans and mice revealed a so far unexpected role of brown adipose tissue in whole body catabolism of BCAAs 31 . Given the inverse correlation between VAT and brown adipose tissue mass 32 one might speculate that this mechanism contributed to our observations as well. Increased BCAA availability, irrespective of the source (e.g.…”

Section: Discussionmentioning

confidence: 69%

Associations between adipose tissue volume and small molecules in plasma and urine among asymptomatic subjects from the general population

Otto

Budde

Kastenmüller

et al. 2020

Sci Rep

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obesity is one of the major risk factor for cardiovascular and metabolic diseases. A disproportional accumulation of fat at visceral (VAt) compared to subcutaneous sites (SAt) has been suspected as a key detrimental event. We used non-targeted metabolomics profiling to reveal metabolic pathways associated with higher VAt or SAt amount among subjects free of metabolic diseases to identify possible contributing metabolic pathways. The study population comprised 491 subjects [mean (standard deviation): age 44.6 yrs (13.0), body mass index 25.4 kg/m² (3.6), 60.1% females] without diabetes, hypertension, dyslipidemia, the metabolic syndrome or impaired renal function. We associated MRi-derived fat amounts with mass spectrometry-derived metabolites in plasma and urine using linear regression models adjusting for major confounders. We tested for sex-specific effects using interactions terms and performed sensitivity analyses for the influence of insulin resistance on the results. VAT and SAT were significantly associated with 155 (101 urine) and 49 (29 urine) metabolites, respectively, of which 45 (27 urine) were common to both. Major metabolic pathways were branched-chain amino acid metabolism (partially independent of insulin resistance), surrogate markers of oxidative stress and gut microbial diversity, and cortisol metabolism. We observed a novel positive association between VAt and plasma levels of the potential pharmacological agent piperine. Sex-specific effects were only a few, e.g. the female-specific association between VAT and O-methylascorbate. In brief, higher VAT was associated with an unfavorable metabolite profile in a sample of healthy, mostly non-obese individuals from the general population and only few sex-specific associations became apparent. equal amount of unknown compounds showed significant associations with VAT, including those related to either cortisol or piperine in the derived metabolic network (Fig. 3).Plasma and urine metabolites associated with SAT. Almost all association between SAT and metabolites were already described for VAT. Within each fluid, only two significant observations were unique to SAT (Figs. 1 and 2). Cortisol (inversely) and N1-methyl-2-pyridone-5-carboxamide (positively) levels in plasma as well as 3′-sialyllactose and the unknown compound X-12840 (both positively) levels in urine associated with SAT.

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Correlation of Brown Adipose Tissue with Other Body Fat Compartments and Patient Characteristics

Cited by 63 publications

References 44 publications

Investigation of the Relationship between MR-Based Supraclavicular Fat Fraction and Thyroid Hormones

Investigation of the Relationship between MR-Based Supraclavicular Fat Fraction and Thyroid Hormones

Adaptor protein APPL1 coordinates HDAC3 to modulate brown adipose tissue thermogenesis in mice

Associations between adipose tissue volume and small molecules in plasma and urine among asymptomatic subjects from the general population

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