Therapeutic value of brown adipose tissue

Gunawardana, Subhadra C.

doi:10.4161/adip.21042

Cited by 8 publications

(8 citation statements)

References 62 publications

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“…Brown adipocytes are the major constituents of brown adipose tissue (BAT), which is situated in the interscapular, cervical, mediastinal and retroperitoneal regions [3,4]. BAT plays a prominent role in thermogenesis and energy expenditure [5]. In 1976, Ricquier et al found a particular 32,000 Mr membranous protein in rat BAT mitochondria, which was upregulated upon cold exposure [6].…”

Section: Introductionmentioning

confidence: 99%

Comprehensive proteomics and functional annotation of mouse brown adipose tissue

Zhao

et al. 2020

PLoS ONE

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Knowledge about the mouse brown adipose tissue (BAT) proteome can provide a deeper understanding of the function of mammalian BAT. Herein, a comprehensive analysis of interscapular BAT from C57BL/6J female mice was conducted by 2DLC and high-resolution mass spectrometry to construct a comprehensive proteome dataset of mouse BAT proteins. A total of 4949 nonredundant proteins were identified, and 4495 were quantified using the iBAQ method. According to the iBAQ values, the BAT proteome was divided into high-, middle-and low-abundance proteins. The functions of the high-abundance proteins were mainly related to glucose and fatty acid oxidation to produce heat for thermoregulation, while the functions of the middle-and low-abundance proteins were mainly related to protein synthesis and apoptosis, respectively. Additionally, 497 proteins were predicted to have signal peptides using SignalP4 software, and 75 were confirmed in previous studies. This study, for the first time, comprehensively profiled and functionally annotated the BAT proteome. This study will be helpful for future studies focused on biomarker identification and BAT molecular mechanisms.

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Section: Introductionmentioning

confidence: 99%

Comprehensive proteomics and functional annotation of mouse brown adipose tissue

Zhao

et al. 2020

PLoS ONE

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“…In addition, much effort has been made to identify human brown adipose-derived stem cells [35], or manipulate human pluripotent stem cells (embryonic stem cells) into brown-specific progenitor cells [36,37]. These classical brown adipocyte models have significantly contributed to the identification of the transcriptional regulatory pathways of brown adipocytes and possess great therapeutic potential for the treatment of obesity [38]. However, classical brown adipocyte cultures are not an attractive model for studying human adaptive thermogenesis due to the paucity of classical BAT in humans; even in infants, beige adipocytes seem to be more prevalent than classical brown fat [7,17].…”

Section: Discussionmentioning

confidence: 99%

BMP7 Drives Human Adipogenic Stem Cells into Metabolically Active Beige Adipocytes

Okla

Temel

et al. 2014

Lipids

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Adult humans have a substantial amount of inducible-brown (or beige) fat, which is associated with increased energy expenditure and reduced weight gain via thermogenesis. Despite the identification of key regulators of beige adipogenesis, impacts of dietary factors on adaptive thermogenesis are largely unknown, partly due to a lack of validated human cell models. Bone morphogenetic protein 7 (BMP7) is known to promote brown adipogenesis in rodent and human progenitor cells. However, controversy still surrounds the cellular identity in BMP7-mediated transition of white to brown adipocytes. The aim of this study is to confirm BMP7-derived human adipocytes as a relevant in vitro model of human beige adipocyte by verifying the cellular lineage and metabolic activity. In this study, we hypothesized that pre-exposure of stromal vascular (SV) fraction of primary human adipogenic precursor cells (hASC) to BMP7 would convert metabolically active brown adipocytes. Our results showed that exposure of hASC to human BMP7 was associated with significant escalation of 1) UCP1 gene expression, a signature gene of brown adipocytes, 2) beige specific marker gene expression (i.e., CD137 and TMEM26), 3) glucose and fatty acid uptake, and 4) basal and cAMP-stimulated oxygen consumption rate compared to white adipocyte control. Taken together, we demonstrated that BMP7 mediates conversion of hASC into metabolically active beige adipocytes. By confirming the cellular identity and metabolic activity, this BMP7-induced human beige adipocytes from hASC should aid in the discovery and assessment of bioactive molecules to promote adaptive thermogenesis.

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“…Recently there has been a plethora of research investigating ways to enhance the expression of thermogenes in WAT. The resulting beige tissue is hypothesized to combat obesity by reducing lipids stored within WAT and increasing energy expenditure [2], [3], [5], [21], [22]. These attempts to induce beige fat necessitate the development of sensitive and specific, translatable, imaging methodologies to accurately detect beige fat mass in vivo .…”

Section: Discussionmentioning

confidence: 99%

“…Metabolically active brown adipose tissue (BAT) plays a significant role in metabolism and energy regulation [1], [2], [3]. While white adipose tissue (WAT) is responsible for energy storage, BAT is responsible for dissipating energy through the action of the uncoupling protein-1 (UCP1).…”

Section: Introductionmentioning

confidence: 99%

Imaging adipose tissue browning using the TSPO-18kDa tracer [18F]FEPPA

Hartimath

Khanapur

Boominathan

et al. 2019

Molecular Metabolism

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Objectives The browning of white adipose tissue (WAT) into beige has been proposed as a strategy to enhance energy expenditure to combat the growing epidemic of obesity. Research into browning strategies are hampered by the lack of sensitive, translatable, imaging tools capable of detecting beige fat mass non-invasively. [ 18 F]FDG is able to detect activated beige fat but provides little information on unstimulated beige fat mass. We have assessed the use of [ 18 F]FEPPA, a tracer for the TSPO-18KDa found on the outer mitochondrial membrane, as an alternative imaging agent capable of detecting unstimulated brown fat (BAT) and beige fat. Methods Female Balb/c mice (n = 5) were treated for 7 days with the β3 adrenergic agonist CL-316,243 to induce the browning of inguinal WAT (beige fat). Animals were imaged longitudinally with [ 18 F]FDG and [ 18 F]FEPPA and uptake in interscapular BAT and inguinal WAT assessed. The browning of inguinal WAT was confirmed using H&E and immunohistochemical detection of UCP-1 and TSPO. Results Repeated dosing with β3-adrenergic agonist CL-316,243 caused a significant increase in [ 18 F]FDG uptake in both interscapular BAT and inguinal WAT associated with the increased metabolic activity of brown and beige adipocytes respectively. [ 18 F]FEPPA uptake was likewise increased in inguinal WAT but showed no increase in BAT uptake due to stimulation over the same time course. Furthermore, inguinal WAT uptake was unaffected by pharmacological blockade, indicating that [ 18 F]FEPPA uptake is associated with the expression of mitochondria in BAT and beige adipocytes and independent of activation. Conclusion These data show that [ 18 F]FEPPA can detect BAT and newly formed beige fat under non-stimulated, thermoneutral conditions and that uptake after stimulation is linked to mitochondrial expression as opposed to activation.

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Therapeutic value of brown adipose tissue

Cited by 8 publications

References 62 publications

Comprehensive proteomics and functional annotation of mouse brown adipose tissue

Comprehensive proteomics and functional annotation of mouse brown adipose tissue

BMP7 Drives Human Adipogenic Stem Cells into Metabolically Active Beige Adipocytes

Imaging adipose tissue browning using the TSPO-18kDa tracer [18F]FEPPA

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