BATLAS: Deconvoluting Brown Adipose Tissue

Perdikari, Aliki; Leparc, Germán; Baláž, Miroslav; Pires, Nuno D.; Lidell, Martin E.; Sun, Wenfei; Fernández-Albert, Francesc; Müller, Sebastian; Akchiche, Nassila; Dong, Hua; Balážová, Lucia; Opitz, Lennart; Röder, Eva; Klein, H.; Štefanička, Patrik; Varga, Lukáš; Nuutila, Pirjo; Virtanen, Kirsi A.; Niemi, Tarja; Taittonen, Markku; Rudofsky, Gottfried; Ukropec, Jozef; Enerbäck, Sven; Stupka, Elia; Neubauer, Heike; Wolfrum, Christian

doi:10.1016/j.celrep.2018.09.044

Cited by 100 publications

(124 citation statements)

References 62 publications

Supporting

Mentioning

110

Contrasting

Order By: Relevance

“…Eighty genes were expressed higher in brown adipocytes irrespective to their anatomical origin and they displayed enrichment of the PPAR signaling pathway (Figures 5A-C). Regarding the latter glycerol kinase, PCK1, CPT1B were present among BATLAS genes [21], PLIN5 was linked to browning [39], ANGPTL4 had not been investigated yet in this respect. In an earlier report Loft et al claimed that browning of human adipocytes, induced by PPARγ stimulation by rosiglitazone of stem cells isolated from prepubic fat pad of a 4-month-old male donor, required the metabolic regulator Kruppel-like factor 11 (KLF11) and reprogramming of a PPARγ super-enhancer [40].…”

Section: Shared Pparγ Mediated Gene Expression Patterns In Dn and Sc mentioning

confidence: 99%

“…The ratio of brown and white adipocytes is partially determined during the early differentiation of mesenchymal progenitors into adipocyte subtypes which is strongly influenced by genetic predisposition [19,20]. This can be quantified in a given tissue or cell culture sample by determining BATLAS score based on the expression of 98 brown and 21 white-specific genes, which were selected by a combined analysis of gene expression signatures in mouse brown, beige and white adipocytes and human tissue samples [21]. Similarly, browning probability can be estimated by a recently developed computational tool, ProFAT [22].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

FTO intronic SNP strongly influences human neck adipocyte browning determined by tissue and PPARγ specific regulation: a transcriptome analysis

Tóth

Arianti

Shaw

et al. 2020

Preprint

View full text Add to dashboard Cite

AbstractBrown adipocytes, abundant in deep-neck (DN) area in humans, are thermogenic with anti-obesity potential. FTO pro-obesity rs1421085 T-to-C SNP shifts differentiation program towards white adipocytes in subcutaneous fat. Human adipose-derived stromal cells were obtained from subcutaneous neck (SC) and DN fat of 9 donors, of which 3-3 carried risk-free (T/T), heterozygous or obesity-risk (C/C) FTO genotypes. They were differentiated to white and brown (long-term PPARγ stimulation) adipocytes, then global RNA sequencing was performed and differentially expressed genes (DEGs) were compared. DN and SC progenitors had similar adipocyte differentiation potential but differed in DEGs. DN adipocytes displayed higher browning features according to ProFAT or BATLAS scores and characteristic DEG patterns revealing associated pathways which were highly expressed (thermogenesis, interferon, cytokine, retinoic acid, with UCP1 and BMP4 as prominent network stabilizers) or downregulated (particularly extracellular matrix remodelling) compared to SC ones. Part of DEGs in either DN or SC browning was PPARγ-dependent. Presence of the FTO obesity-risk allele suppressed the expression of mitochondrial and thermogenesis genes with a striking resemblance between affected pathways and those appearing in ProFAT and BATLAS, underlining the importance of metabolic and mitochondrial pathways in thermogenesis. Among overlapping regulatory influences which determine browning and thermogenic potential of neck adipocytes, FTO genetic background has a so far not recognized prominence.

show abstract

Section: Shared Pparγ Mediated Gene Expression Patterns In Dn and Sc mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

FTO intronic SNP strongly influences human neck adipocyte browning determined by tissue and PPARγ specific regulation: a transcriptome analysis

Tóth

Arianti

Shaw

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…to reduce body weight by 16.5% (primarily due to fat loss) promoted the brown adipocyte content in subcutaneous fat by 10%. 26 At the same time, fasting blood insulin and glucose were improved. Furthermore, in humans, brown fat appears to exhibit a glucose responsive biorhythm that is disrupted when the abundance of brown fat is low.…”

Section: What Is the Contribution Of Brown Fat To Whole Body Glucose mentioning

confidence: 90%

Brown adipose tissue and glucose homeostasis – the link between climate change and the global rise in obesity and diabetes

et al. 2018

View full text Add to dashboard Cite

REVIEWBrown adipose tissue and glucose homeostasisthe link between climate change and the global rise in obesity and diabetes ABSTRACT There is increasing evidence that the global rise in temperature is contributing to the onset of diabetes, which could be mediated by a concomitant reduction in brown fat activity. Brown (and beige) fat are characterised as possessing a unique mitochondrial protein uncoupling protein (UCP)1 that when activated can rapidly generate large amounts of heat. Primary environmental stimuli of UCP1 include cold-exposure and diet, leading to increased activity of the sympathetic nervous system and large amounts of lipid and glucose being oxidised by brown fat. The exact contribution remains controversial, although recent studies indicate that the amount of brown and beige fat in adult humans has been greatly underestimated. We therefore review the potential mechanisms by which glucose could be utilised within brown and beige fat in adult humans and the extent to which these are sensitive to temperature and diet. This includes the potential contribution from the peridroplet and cytoplasmic mitochondrial sub-fractions recently identified in brown fat, and whether a proportion of glucose oxidation could be UCP1independent. It is thus predicted that as new methods are developed to assess glucose metabolism by brown fat, a more accurate determination of the thermogenic and non-thermogenic functions could be feasible in humans. ARTICLE HISTORY

show abstract

“…Paired samples of deep neck BAT and adjacent subcutaneous WAT were obtained from patients undergoing neck surgery under general anesthesia, as described in 18–19 . We analyzed tissues from 36 patients [ gender 5M/31F, age 43.5±14.5 years, body mass index 25.9±4.2 kg.m −2 , waist 87.6±12.8 cm, body fat 32.4±9.1 % (bioelectrical impedance, Omron BF511, Japan), fasting plasma glucose: 4.78±1.00 mmol.l −1 , triglycerides: 1.35±0.44 mmol.l −1 , HDL cholesterol: 1.43±0.41 mmol.l −1 , PTH: 74.15±38.50 pg.ml −1 ].…”

Section: Methodsmentioning

confidence: 99%

Cold exposure distinctively modulates parathyroid and thyroid hormones in cold-acclimatized and non-acclimatized humans

Kovaničová

Kurdiová

Baláž

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

AbstractContextCold-induced activation of thermogenesis modulates energy metabolism, but the role of humoral mediators is not completely understood.ObjectiveTo investigate the role of parathyroid and thyroid hormones in acute and adaptive response to cold in humans.DesignCross-sectional study examining acute response to ice-water swimming and to experimental non-shivering thermogenesis (NST) induction in individuals acclimatized and non-acclimatized to cold. Seasonal variation in energy metabolism of ice-water swimmers and associations between circulating PTH and molecular components of thermogenic program in brown adipose tissue (BAT) of neck-surgery patients were evaluated.SettingClinical Research Center.Patients, ParticipantsIce-water swimmers (winter swim n=15, NST-induction n=6), non-acclimatized volunteers (NST-induction, n=11, elective neck surgery n = 36).Main Outcomes and ResultsIn ice-water swimmers, PTH and TSH increased in response to 15min winter swim, while activation of NST failed to regulate PTH and lowered TSH. In non-acclimatized men, NST-induction decreased PTH and TSH. Positive correlation between systemic levels of PTH and whole-body metabolic preference for lipids as well as BAT 18F-FDG uptake was found across the two populations. Moreover, NST-cooling protocol-induced changes in metabolic preference for lipids correlated positively with changes in PTH. Finally, variability in circulating PTH correlated positively with UCP1/UCP1, PPARGC1A and DIO2 in BAT from neck surgery patients.ConclusionsRegulation of PTH and thyroid hormones during cold exposure in humans depends on the cold acclimatization level and/or cold stimulus intensity. Role of PTH in NST is substantiated by its positive relationships with whole-body metabolic preference for lipids, BAT volume and UCP1 content.

show abstract

BATLAS: Deconvoluting Brown Adipose Tissue

Cited by 100 publications

References 62 publications

FTO intronic SNP strongly influences human neck adipocyte browning determined by tissue and PPARγ specific regulation: a transcriptome analysis

FTO intronic SNP strongly influences human neck adipocyte browning determined by tissue and PPARγ specific regulation: a transcriptome analysis

Brown adipose tissue and glucose homeostasis – the link between climate change and the global rise in obesity and diabetes

Cold exposure distinctively modulates parathyroid and thyroid hormones in cold-acclimatized and non-acclimatized humans

Contact Info

Product

Resources

About