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Article ; Online: Blood Sampling for Arteriovenous Difference Measurements Across Interscapular Brown Adipose Tissue in Rat.

Mestres-Arenas, Alberto / Cairó, Montserrat / Peyrou, Marion / Villarroya, Francesc

Methods in molecular biology (Clifton, N.J.)

2022 Volume 2448, Page(s) 273–282

Abstract: A classic physiological approach to assess the specific uptake or release of circulating factors in organs and tissues is to measure concentration differences between venous and arterial blood. For interscapular brown adipose tissue (iBAT), the anatomic ... ...

Abstract	A classic physiological approach to assess the specific uptake or release of circulating factors in organs and tissues is to measure concentration differences between venous and arterial blood. For interscapular brown adipose tissue (iBAT), the anatomic distribution of its vascularization, which drains most of the blood into Sulzer's vein, allows for local measurement of arteriovenous differences. The use of this procedure to monitor oxygen concentration changes was fundamental for the recognition of BAT as the main site of adaptive non-shivering thermogenesis. More recently, this technique has regained importance as a means to identify BAT-secreted regulatory molecules, such as fibroblast growth factor-21 and the chemokine CXCL14. In this chapter, we provide a detailed description of an optimized and feasible protocol to determine arteriovenous differences across iBAT. We include tips and practical advice for using this powerful tool to study BAT metabolism and secretory activity in rats as an experimental model.
MeSH term(s)	Adipose Tissue, Brown ; Animals ; Rats ; Thermogenesis ; Veins
Language	English
Publishing date	2022-03-04
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-2087-8_17
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Article: A Differential Pattern of Batokine Expression in Perivascular Adipose Tissue Depots From Mice.

Mestres-Arenas, Alberto / Villarroya, Joan / Giralt, Marta / Villarroya, Francesc / Peyrou, Marion

Frontiers in physiology

2021 Volume 12, Page(s) 714530

Abstract: Depending on its anatomical placement, perivascular adipose tissue (PVAT) has been found to possess features more (e.g., aortic thoracic) or less (e.g., aortic abdominal) similar to brown/beige adipose tissue in mice, whereas PVAT surrounding the ... ...

Abstract	Depending on its anatomical placement, perivascular adipose tissue (PVAT) has been found to possess features more (e.g., aortic thoracic) or less (e.g., aortic abdominal) similar to brown/beige adipose tissue in mice, whereas PVAT surrounding the mesenteric arteries and the caudal part of abdominal aorta is similar to white fat. PVAT is thought to influence vascular function through the effects of adipose-secreted molecules on vessels. Brown adipose tissue was recently shown to play differential secretory role
Language	English
Publishing date	2021-08-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2021.714530
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Article ; Online: Transcriptional regulation of the uncoupling protein-1 gene.

Villarroya, Francesc / Peyrou, Marion / Giralt, Marta

Biochimie

2017 Volume 134, Page(s) 86–92

Abstract: Regulated transcription of the uncoupling protein-1 (UCP1) gene, and subsequent UCP1 protein synthesis, is a hallmark of the acquisition of the differentiated, thermogenically competent status of brown and beige/brite adipocytes, as well as of the ... ...

Abstract	Regulated transcription of the uncoupling protein-1 (UCP1) gene, and subsequent UCP1 protein synthesis, is a hallmark of the acquisition of the differentiated, thermogenically competent status of brown and beige/brite adipocytes, as well as of the responsiveness of brown and beige/brite adipocytes to adaptive regulation of thermogenic activity. The 5' non-coding region of the UCP1 gene contains regulatory elements that confer tissue specificity, differentiation dependence, and neuro-hormonal regulation to UCP1 gene transcription. Two main regions-a distal enhancer and a proximal promoter region-mediate transcriptional regulation through interactions with a plethora of transcription factors, including nuclear hormone receptors and cAMP-responsive transcription factors. Co-regulators, such as PGC-1α, play a pivotal role in the concerted regulation of UCP1 gene transcription. Multiple interactions of transcription factors and co-regulators at the promoter region of the UCP1 gene result in local chromatin remodeling, leading to activation and increased accessibility of RNA polymerase II and subsequent gene transcription. Moreover, a commonly occurring A-to-G polymorphism in close proximity to the UCP1 gene enhancer influences the extent of UCP1 gene transcription. Notably, it has been reported that specific aspects of obesity and associated metabolic diseases are associated with human population variability at this site. On another front, the unique properties of the UCP1 promoter region have been exploited to develop brown adipose tissue-specific gene delivery tools for experimental purposes.
MeSH term(s)	Adipose Tissue, Beige/cytology ; Adipose Tissue, Beige/metabolism ; Adipose Tissue, Brown/cytology ; Adipose Tissue, Brown/metabolism ; Adipose Tissue, White/cytology ; Adipose Tissue, White/metabolism ; Animals ; Gene Expression Regulation ; Humans ; Mice ; Obesity/genetics ; Obesity/metabolism ; Obesity/pathology ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism ; Promoter Regions, Genetic ; RNA Polymerase II/genetics ; RNA Polymerase II/metabolism ; Receptors, Cytoplasmic and Nuclear/genetics ; Receptors, Cytoplasmic and Nuclear/metabolism ; Thermogenesis/genetics ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Transcription, Genetic ; Uncoupling Protein 1/genetics ; Uncoupling Protein 1/metabolism
Chemical Substances	PPARGC1A protein, human ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; Receptors, Cytoplasmic and Nuclear ; Transcription Factors ; UCP1 protein, human ; Uncoupling Protein 1 ; RNA Polymerase II (EC 2.7.7.-)
Language	English
Publishing date	2017-03
Publishing country	France
Document type	Journal Article ; Review
ZDB-ID	120345-9
ISSN	1638-6183 ; 0300-9084
ISSN (online)	1638-6183
ISSN	0300-9084
DOI	10.1016/j.biochi.2016.09.017
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Article ; Online: Scalable Generation of Pre-Vascularized and Functional Human Beige Adipose Organoids.

Escudero, Mélanie / Vaysse, Laurence / Eke, Gozde / Peyrou, Marion / Villarroya, Francesc / Bonnel, Sophie / Jeanson, Yannick / Boyer, Louisa / Vieu, Christophe / Chaput, Benoit / Yao, Xi / Deschaseaux, Frédéric / Parny, Mélissa / Raymond-Letron, Isabelle / Dani, Christian / Carrière, Audrey / Malaquin, Laurent / Casteilla, Louis

Advanced science (Weinheim, Baden-Wurttemberg, Germany)

2023 Volume 10, Issue 31, Page(s) e2301499

Abstract: Obesity and type 2 diabetes are becoming a global sociobiomedical burden. Beige adipocytes are emerging as key inducible actors and putative relevant therapeutic targets for improving metabolic health. However, in vitro models of human beige adipose ... ...

Abstract	Obesity and type 2 diabetes are becoming a global sociobiomedical burden. Beige adipocytes are emerging as key inducible actors and putative relevant therapeutic targets for improving metabolic health. However, in vitro models of human beige adipose tissue are currently lacking and hinder research into this cell type and biotherapy development. Unlike traditional bottom-up engineering approaches that aim to generate building blocks, here a scalable system is proposed to generate pre-vascularized and functional human beige adipose tissue organoids using the human stromal vascular fraction of white adipose tissue as a source of adipose and endothelial progenitors. This engineered method uses a defined biomechanical and chemical environment using tumor growth factor β (TGFβ) pathway inhibition and specific gelatin methacryloyl (GelMA) embedding parameters to promote the self-organization of spheroids in GelMA hydrogel, facilitating beige adipogenesis and vascularization. The resulting vascularized organoids display key features of native beige adipose tissue including inducible Uncoupling Protein-1 (UCP1) expression, increased uncoupled mitochondrial respiration, and batokines secretion. The controlled assembly of spheroids allows to translate organoid morphogenesis to a macroscopic scale, generating vascularized centimeter-scale beige adipose micro-tissues. This approach represents a significant advancement in developing in vitro human beige adipose tissue models and facilitates broad applications ranging from basic research to biotherapies.
MeSH term(s)	Humans ; Diabetes Mellitus, Type 2/metabolism ; Obesity/metabolism ; Adipogenesis ; Adipose Tissue, White/metabolism ; Organoids/metabolism
Language	English
Publishing date	2023-09-20
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2808093-2
ISSN	2198-3844 ; 2198-3844
ISSN (online)	2198-3844
ISSN	2198-3844
DOI	10.1002/advs.202301499
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Article ; Online: New insights into the secretory functions of brown adipose tissue.

Villarroya, Joan / Cereijo, Rubén / Gavaldà-Navarro, Aleix / Peyrou, Marion / Giralt, Marta / Villarroya, Francesc

The Journal of endocrinology

2019 Volume 243, Issue 2, Page(s) R19–R27

Abstract: In recent years, an important secretory role of brown adipose tissue (BAT) has emerged, which is consistent, to some extent, with the earlier recognition of the important secretory role of white fat. The so-called brown adipokines or 'batokines' may play ...

Abstract	In recent years, an important secretory role of brown adipose tissue (BAT) has emerged, which is consistent, to some extent, with the earlier recognition of the important secretory role of white fat. The so-called brown adipokines or 'batokines' may play an autocrine role, which may either be positive or negative, in the thermogenic function of brown adipocytes. Additionally, there is a growing recognition of the signalling molecules released by brown adipocytes that target sympathetic nerve endings (such as neuregulin-4 and S100b protein), vascular cells (e.g., bone morphogenetic protein-8b), and immune cells (e.g., C-X-C motif chemokine ligand-14) to promote the tissue remodelling associated with the adaptive BAT recruitment in response to thermogenic stimuli. Moreover, existing indications of an endocrine role of BAT are being confirmed through the release of brown adipokines acting on other distant tissues and organs; a recent example is the recognition that BAT-secreted fibroblast growth factor-21 and myostatin target the heart and skeletal muscle, respectively. The application of proteomics technologies is aiding the identification of new members of the brown adipocyte secretome, such as the extracellular matrix or complement system components. In summary, BAT can no longer be considered a mere producer of heat in response to environment or dietary challenges; it is also an active secretory tissue releasing brown adipokines with a relevant local and systemic action. The identification of the major brown adipokines and their roles is highly important for the discovery of novel candidates useful in formulating intervention strategies for metabolic diseases.
MeSH term(s)	Adipocytes, Brown/metabolism ; Adipokines/metabolism ; Adipose Tissue, Brown/cytology ; Adipose Tissue, Brown/metabolism ; Animals ; Autocrine Communication/physiology ; Energy Metabolism/physiology ; Fibroblast Growth Factors/metabolism ; Humans ; Metabolic Diseases/diagnosis ; Metabolic Diseases/physiopathology ; Metabolic Diseases/therapy ; Thermogenesis/physiology
Chemical Substances	Adipokines ; fibroblast growth factor 21 ; Fibroblast Growth Factors (62031-54-3)
Language	English
Publishing date	2019-07-31
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	3028-4
ISSN	1479-6805 ; 0022-0795
ISSN (online)	1479-6805
ISSN	0022-0795
DOI	10.1530/JOE-19-0295
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Article: Brown Adipokines.

Villarroya, Francesc / Gavaldà-Navarro, Aleix / Peyrou, Marion / Villarroya, Joan / Giralt, Marta

Handbook of experimental pharmacology

2018 Volume 251, Page(s) 239–256

Abstract: Brown adipokines are regulatory factors secreted by brown and beige adipocytes that exhibit endocrine, paracrine, and autocrine actions. Peptidic and non-peptidic molecules, including miRNAs and lipids, are constituents of brown adipokines. Brown adipose ...

Abstract	Brown adipokines are regulatory factors secreted by brown and beige adipocytes that exhibit endocrine, paracrine, and autocrine actions. Peptidic and non-peptidic molecules, including miRNAs and lipids, are constituents of brown adipokines. Brown adipose tissue remodeling to meet thermogenic needs is dependent on the secretory properties of brown/beige adipocytes. The association between brown fat activity and a healthy metabolic profile, in relation to energy balance and glucose and lipid homeostasis, is influenced by the endocrine actions of brown adipokines. A comprehensive knowledge of the brown adipocyte secretome is still lacking. Advancements in the identification and characterization of brown adipokines will facilitate therapeutic interventions for metabolic diseases, as these molecules are obvious candidates to therapeutic agents. Moreover, identification of brown adipokines as circulating biomarkers of brown adipose tissue activity may be particularly useful for noninvasive assessment of brown adipose tissue alterations in human pathologies.
MeSH term(s)	Adipocytes, Brown/metabolism ; Adipokines/metabolism ; Adipose Tissue, Brown/metabolism ; Energy Metabolism ; Humans ; Thermogenesis/physiology
Chemical Substances	Adipokines
Language	English
Publishing date	2018-04-19
Publishing country	Germany
Document type	Journal Article
ISSN	0171-2004
ISSN	0171-2004
DOI	10.1007/164_2018_119
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Article ; Online: Scalable Generation of Pre‐Vascularized and Functional Human Beige Adipose Organoids

Mélanie Escudero / Laurence Vaysse / Gozde Eke / Marion Peyrou / Francesc Villarroya / Sophie Bonnel / Yannick Jeanson / Louisa Boyer / Christophe Vieu / Benoit Chaput / Xi Yao / Frédéric Deschaseaux / Mélissa Parny / Isabelle Raymond‐Letron / Christian Dani / Audrey Carrière / Laurent Malaquin / Louis Casteilla

Advanced Science, Vol 10, Iss 31, Pp n/a-n/a (2023)

2023

Abstract: Abstract Obesity and type 2 diabetes are becoming a global sociobiomedical burden. Beige adipocytes are emerging as key inducible actors and putative relevant therapeutic targets for improving metabolic health. However, in vitro models of human beige ... ...

Abstract	Abstract Obesity and type 2 diabetes are becoming a global sociobiomedical burden. Beige adipocytes are emerging as key inducible actors and putative relevant therapeutic targets for improving metabolic health. However, in vitro models of human beige adipose tissue are currently lacking and hinder research into this cell type and biotherapy development. Unlike traditional bottom‐up engineering approaches that aim to generate building blocks, here a scalable system is proposed to generate pre‐vascularized and functional human beige adipose tissue organoids using the human stromal vascular fraction of white adipose tissue as a source of adipose and endothelial progenitors. This engineered method uses a defined biomechanical and chemical environment using tumor growth factor β (TGFβ) pathway inhibition and specific gelatin methacryloyl (GelMA) embedding parameters to promote the self‐organization of spheroids in GelMA hydrogel, facilitating beige adipogenesis and vascularization. The resulting vascularized organoids display key features of native beige adipose tissue including inducible Uncoupling Protein‐1 (UCP1) expression, increased uncoupled mitochondrial respiration, and batokines secretion. The controlled assembly of spheroids allows to translate organoid morphogenesis to a macroscopic scale, generating vascularized centimeter‐scale beige adipose micro‐tissues. This approach represents a significant advancement in developing in vitro human beige adipose tissue models and facilitates broad applications ranging from basic research to biotherapies.
Keywords	adipose‐derived stroma/stem cells (ASC) ; beige and brown adipocytes ; guided‐assembly ; hydrogels ; microtissues ; organoid morphogenesis ; Science ; Q
Subject code	571
Language	English
Publishing date	2023-11-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
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Article ; Online: Adipose tissue plasticity in pheochromocytoma patients suggests a role of the splicing machinery in human adipose browning.

Castellá, Moisés / Blasco-Roset, Albert / Peyrou, Marion / Gavaldà-Navarro, Aleix / Villarroya, Joan / Quesada-López, Tania / Lorente-Poch, Leyre / Sancho, Juan / Szymczak, Florian / Piron, Anthony / Rodríguez-Fernández, Sonia / Carobbio, Stefania / Goday, Albert / Domingo, Pere / Vidal-Puig, Antonio / Giralt, Marta / Eizirik, Décio L / Villarroya, Francesc / Cereijo, Rubén

iScience

2023 Volume 26, Issue 6, Page(s) 106847

Abstract: Adipose tissue from pheochromocytoma patients acquires brown fat features, making it a valuable model for studying the mechanisms that control thermogenic adipose plasticity in humans. Transcriptomic analyses revealed a massive downregulation of splicing ...

Abstract	Adipose tissue from pheochromocytoma patients acquires brown fat features, making it a valuable model for studying the mechanisms that control thermogenic adipose plasticity in humans. Transcriptomic analyses revealed a massive downregulation of splicing machinery components and splicing regulatory factors in browned adipose tissue from patients, with upregulation of a few genes encoding RNA-binding proteins potentially involved in splicing regulation. These changes were also observed in cell culture models of human brown adipocyte differentiation, confirming a potential involvement of splicing in the cell-autonomous control of adipose browning. The coordinated changes in splicing are associated with a profound modification in the expression levels of splicing-driven transcript isoforms for genes involved in the specialized metabolism of brown adipocytes and those encoding master transcriptional regulators of adipose browning. Splicing control appears to be a relevant component of the coordinated gene expression changes that allow human adipose tissue to acquire a brown phenotype.
Language	English
Publishing date	2023-05-09
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2023.106847
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Article ; Online: GDF11 inhibits adipogenesis and improves mature adipocytes metabolic function via WNT/β-catenin and ALK5/SMAD2/3 pathways.

Frohlich, Jan / Kovacovicova, Kristina / Raffaele, Marco / Virglova, Tereza / Cizkova, Eliska / Kucera, Jan / Bienertova-Vasku, Julie / Wabitsch, Martin / Peyrou, Marion / Bonomini, Francesca / Rezzani, Rita / Chaldakov, George N / Tonchev, Anton B / Di Rosa, Michelino / Blavet, Nicolas / Hejret, Vaclav / Vinciguerra, Manlio

Cell proliferation

2022 Volume 55, Issue 10, Page(s) e13310

Abstract: Objective: GDF11 is a member of the TGF-β superfamily that was recently implicated as potential "rejuvenating" factor, which can ameliorate metabolic disorders. The main objective of the presented study was to closely characterize the role of GDF11 ... ...

Abstract	Objective: GDF11 is a member of the TGF-β superfamily that was recently implicated as potential "rejuvenating" factor, which can ameliorate metabolic disorders. The main objective of the presented study was to closely characterize the role of GDF11 signaling in the glucose homeostasis and in the differentiation of white adipose tissue. Methods: We performed microscopy imaging, biochemical and transcriptomic analyses of adipose tissues of 9 weeks old ob/ob mice and murine and human pre-adipocyte cell lines. Results: Our in vivo experiments employing GDF11 treatment in ob/ob mice showed improved glucose/insulin homeostasis, decreased weight gain and white adipocyte size. Furthermore, GDF11 treatment inhibited adipogenesis in pre-adipocytes by ALK5-SMAD2/3 activation in cooperation with the WNT/β-catenin pathway, whose inhibition resulted in adipogenic differentiation. Lastly, we observed significantly elevated levels of the adipokine hormone adiponectin and increased glucose uptake by mature adipocytes upon GDF11 exposure. Conclusion: We show evidence that link GDF11 to adipogenic differentiation, glucose, and insulin homeostasis, which are pointing towards potential beneficial effects of GDF11-based "anti-obesity" therapy.
MeSH term(s)	Adipocytes/metabolism ; Adipogenesis ; Adiponectin/metabolism ; Animals ; Bone Morphogenetic Proteins/metabolism ; Cell Differentiation/physiology ; Glucose/metabolism ; Growth Differentiation Factors/metabolism ; Humans ; Insulin/metabolism ; Mice ; Receptor, Transforming Growth Factor-beta Type I ; Smad Proteins, Receptor-Regulated ; Smad2 Protein ; Smad3 Protein ; Transforming Growth Factor beta/metabolism ; Wnt Signaling Pathway ; beta Catenin/metabolism
Chemical Substances	Adiponectin ; Bone Morphogenetic Proteins ; GDF11 protein, human ; Gdf11 protein, mouse ; Growth Differentiation Factors ; Insulin ; SMAD2 protein, human ; SMAD3 protein, human ; Smad Proteins, Receptor-Regulated ; Smad2 Protein ; Smad2 protein, mouse ; Smad3 Protein ; Smad3 protein, mouse ; Transforming Growth Factor beta ; beta Catenin ; Receptor, Transforming Growth Factor-beta Type I (EC 2.7.11.30) ; TGFBR1 protein, human (EC 2.7.11.30) ; Tgfbr1 protein, mouse (EC 2.7.11.30) ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2022-08-03
Publishing country	England
Document type	Journal Article
ZDB-ID	1064202-x
ISSN	1365-2184 ; 0008-8730 ; 0960-7722
ISSN (online)	1365-2184
ISSN	0008-8730 ; 0960-7722
DOI	10.1111/cpr.13310
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Article ; Online: Statins may protect against hepatocellular carcinoma development in patients infected with hepatitis C virus, but what are the mechanisms?

Clément, Sophie / Peyrou, Marion / Foti, Michelangelo / Negro, Francesco

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

2013 Volume 31, Issue 32, Page(s) 4160–4161

MeSH term(s)	Carcinoma, Hepatocellular/etiology ; Female ; Hepatitis C/complications ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects ; Liver Neoplasms/etiology ; Male
Chemical Substances	Hydroxymethylglutaryl-CoA Reductase Inhibitors
Language	English
Publishing date	2013-11-10
Publishing country	United States
Document type	Comment ; Letter
ZDB-ID	604914-x
ISSN	1527-7755 ; 0732-183X
ISSN (online)	1527-7755
ISSN	0732-183X
DOI	10.1200/JCO.2013.51.0354
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