دورية أكاديمية
Mouse vascularized adipose spheroids: an organotypic model for thermogenic adipocytes.
العنوان: | Mouse vascularized adipose spheroids: an organotypic model for thermogenic adipocytes. |
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المؤلفون: | Davidsen LI; Functional Genomics and Metabolism Research Unit, Institute of Biochemistry and Molecular Biology, Faculty of Science, University of Southern Denmark, Odense, Denmark., Hagberg CE; Division of Cardiovascular Medicine, Department of Medicine Solna and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden., Goitea V; Functional Genomics and Metabolism Research Unit, Institute of Biochemistry and Molecular Biology, Faculty of Science, University of Southern Denmark, Odense, Denmark.; Novo Nordisk Foundation Center for Adipocyte Signaling (ADIPOSIGN), University of Southern Denmark, Odense, Denmark., Lundby SM; Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Larsen S; Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Ebbesen MF; Danish Molecular Biomedical Imaging Center (DaMBIC), Institute of Biochemistry and Molecular Biology, Faculty of Science, University of Southern Denmark, Odense, Denmark., Stanic N; Functional Genomics and Metabolism Research Unit, Institute of Biochemistry and Molecular Biology, Faculty of Science, University of Southern Denmark, Odense, Denmark., Topel H; Functional Genomics and Metabolism Research Unit, Institute of Biochemistry and Molecular Biology, Faculty of Science, University of Southern Denmark, Odense, Denmark.; Novo Nordisk Foundation Center for Adipocyte Signaling (ADIPOSIGN), University of Southern Denmark, Odense, Denmark., Kornfeld JW; Functional Genomics and Metabolism Research Unit, Institute of Biochemistry and Molecular Biology, Faculty of Science, University of Southern Denmark, Odense, Denmark.; Novo Nordisk Foundation Center for Adipocyte Signaling (ADIPOSIGN), University of Southern Denmark, Odense, Denmark. |
المصدر: | Frontiers in endocrinology [Front Endocrinol (Lausanne)] 2024 Jun 25; Vol. 15, pp. 1396965. Date of Electronic Publication: 2024 Jun 25 (Print Publication: 2024). |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101555782 Publication Model: eCollection Cited Medium: Print ISSN: 1664-2392 (Print) Linking ISSN: 16642392 NLM ISO Abbreviation: Front Endocrinol (Lausanne) Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: [Lausanne : Frontiers Research Foundation] |
مواضيع طبية MeSH: | Thermogenesis* , Spheroids, Cellular*/metabolism, Animals ; Mice ; Adipose Tissue, White/metabolism ; Adipose Tissue, White/cytology ; Mice, Inbred C57BL ; Male ; Adipocytes/metabolism ; Adipocytes/cytology ; Adipose Tissue, Brown/metabolism ; Adipose Tissue, Brown/cytology ; Cells, Cultured ; Adipocytes, Beige/metabolism ; Adipocytes, Beige/cytology ; Energy Metabolism ; Adipogenesis/physiology ; Microphysiological Systems |
مستخلص: | Adipose tissues, particularly beige and brown adipose tissue, play crucial roles in energy metabolism. Brown adipose tissues' thermogenic capacity and the appearance of beige cells within white adipose tissue have spurred interest in their metabolic impact and therapeutic potential. Brown and beige fat cells, activated by environmental factors like cold exposure or by pharmacology, share metabolic mechanisms that drive non-shivering thermogenesis. Understanding these two cell types requires advanced, yet broadly applicable in vitro models that reflect the complex microenvironment and vasculature of adipose tissues. Here we present mouse vascularized adipose spheroids of the stromal vascular microenvironment from inguinal white adipose tissue, a tissue with 'beiging' capacity in mice and humans. We show that adding a scaffold improves vascular sprouting, enhances spheroid growth, and upregulates adipogenic markers, thus reflecting increased adipocyte maturity. Transcriptional profiling via RNA sequencing revealed distinct metabolic pathways upregulated in our vascularized adipose spheroids, with increased expression of genes involved in glucose metabolism, lipid metabolism, and thermogenesis. Functional assessment demonstrated increased oxygen consumption in vascularized adipose spheroids compared to classical 2D cultures, which was enhanced by β-adrenergic receptor stimulation correlating with elevated β-adrenergic receptor expression. Moreover, stimulation with the naturally occurring adipokine, FGF21, induced Ucp1 mRNA expression in the vascularized adipose spheroids. In conclusion, vascularized inguinal white adipose tissue spheroids provide a physiologically relevant platform to study how the stromal vascular microenvironment shapes adipocyte responses and influence activated thermogenesis in beige adipocytes. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Davidsen, Hagberg, Goitea, Lundby, Larsen, Ebbesen, Stanic, Topel and Kornfeld.) |
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فهرسة مساهمة: | Keywords: 3D spheroids; adipose tissue microenvironment; browning; crosstalk; metabolism; oxygraph; thermogenesis; vascularization |
تواريخ الأحداث: | Date Created: 20240710 Date Completed: 20240710 Latest Revision: 20240711 |
رمز التحديث: | 20240711 |
مُعرف محوري في PubMed: | PMC11231189 |
DOI: | 10.3389/fendo.2024.1396965 |
PMID: | 38982992 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1664-2392 |
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DOI: | 10.3389/fendo.2024.1396965 |