Transcriptomic signatures of cold acclimated adipocytes reveal CXCL12 as a Brown autocrine and paracrine chemokine
Besides its thermogenic capacity, brown adipose tissue (BAT) performs important secretory functions that regulate metabolism. However, the BAT microenvironment and factors involved in BAT homeostasis and adaptation to cold remain poorly characterized. We therefore aimed to study brown adipocyte-deri...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-03-01
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| Series: | Molecular Metabolism |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212877825000092 |
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| author | Marina Agueda-Oyarzabal Marie S. Isidor Kaja Plucińska Lars R. Ingerslev Oksana Dmytriyeva Patricia S.S. Petersen Sara Laftih Axel B. Pontoppidan Jo B. Henningsen Kaja Rupar Erin L. Brown Thue W. Schwartz Romain Barrès Zachary Gerhart-Hines Camilla C. Schéele Brice Emanuelli |
| author_facet | Marina Agueda-Oyarzabal Marie S. Isidor Kaja Plucińska Lars R. Ingerslev Oksana Dmytriyeva Patricia S.S. Petersen Sara Laftih Axel B. Pontoppidan Jo B. Henningsen Kaja Rupar Erin L. Brown Thue W. Schwartz Romain Barrès Zachary Gerhart-Hines Camilla C. Schéele Brice Emanuelli |
| author_sort | Marina Agueda-Oyarzabal |
| collection | DOAJ |
| description | Besides its thermogenic capacity, brown adipose tissue (BAT) performs important secretory functions that regulate metabolism. However, the BAT microenvironment and factors involved in BAT homeostasis and adaptation to cold remain poorly characterized. We therefore aimed to study brown adipocyte-derived secreted factors that may be involved in adipocyte function and/or may orchestrate intercellular communications. For this, mRNA levels in mature adipocytes from mouse adipose depots were assessed using RNA sequencing upon chronic cold acclimation, and bioinformatic analysis was used to identify secreted factors. Among 858 cold-sensitive transcripts in BAT adipocytes were 210 secreted factor-encoding genes, and Cxcl12 was the top brown adipocyte-enriched cytokine. Cxcl12 mRNA expression analysis by RT-qPCR and fluorescence in situ hybridization specified Cxcl12 distribution in various cell types, and indicated its enrichment in cold-acclimated brown adipocytes. We found that CXCL12 secretion from BAT was increased after chronic cold, yet its level in plasma remained unchanged, suggesting a local/paracrine function. Cxcl12 knockdown in mature brown adipocytes impaired thermogenesis, as assessed by norepinephrine (NE)-induced glycerol release and mitochondrial respiration. However, knockdown of Cxcl12 did not impact β-adrenergic signaling, suggesting that CXCL12 regulates adipocyte function downstream of the β-adrenergic pathway. Moreover, we provide evidence for CXCL12 to exert intercellular cross-talk via its capacity to promote macrophage chemotaxis and neurite outgrowth. Collectively, our results indicate that CXCL12 is a brown adipocyte-enriched, cold-induced secreted factor involved in adipocyte function and the BAT microenvironment communication network. |
| format | Article |
| id | doaj-art-0ae78039501e42c39b1c0421cdc0e5aa |
| institution | Kabale University |
| issn | 2212-8778 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Metabolism |
| spelling | doaj-art-0ae78039501e42c39b1c0421cdc0e5aa2025-02-02T05:27:07ZengElsevierMolecular Metabolism2212-87782025-03-0193102102Transcriptomic signatures of cold acclimated adipocytes reveal CXCL12 as a Brown autocrine and paracrine chemokineMarina Agueda-Oyarzabal0Marie S. Isidor1Kaja Plucińska2Lars R. Ingerslev3Oksana Dmytriyeva4Patricia S.S. Petersen5Sara Laftih6Axel B. Pontoppidan7Jo B. Henningsen8Kaja Rupar9Erin L. Brown10Thue W. Schwartz11Romain Barrès12Zachary Gerhart-Hines13Camilla C. Schéele14Brice Emanuelli15Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Institut de Pharmacologie Moléculaire et Cellulaire, Université Côte d’Azur & Centre National pour la Recherche Scientifique (CNRS), Valbonne, 06560, FranceNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Corresponding author.Besides its thermogenic capacity, brown adipose tissue (BAT) performs important secretory functions that regulate metabolism. However, the BAT microenvironment and factors involved in BAT homeostasis and adaptation to cold remain poorly characterized. We therefore aimed to study brown adipocyte-derived secreted factors that may be involved in adipocyte function and/or may orchestrate intercellular communications. For this, mRNA levels in mature adipocytes from mouse adipose depots were assessed using RNA sequencing upon chronic cold acclimation, and bioinformatic analysis was used to identify secreted factors. Among 858 cold-sensitive transcripts in BAT adipocytes were 210 secreted factor-encoding genes, and Cxcl12 was the top brown adipocyte-enriched cytokine. Cxcl12 mRNA expression analysis by RT-qPCR and fluorescence in situ hybridization specified Cxcl12 distribution in various cell types, and indicated its enrichment in cold-acclimated brown adipocytes. We found that CXCL12 secretion from BAT was increased after chronic cold, yet its level in plasma remained unchanged, suggesting a local/paracrine function. Cxcl12 knockdown in mature brown adipocytes impaired thermogenesis, as assessed by norepinephrine (NE)-induced glycerol release and mitochondrial respiration. However, knockdown of Cxcl12 did not impact β-adrenergic signaling, suggesting that CXCL12 regulates adipocyte function downstream of the β-adrenergic pathway. Moreover, we provide evidence for CXCL12 to exert intercellular cross-talk via its capacity to promote macrophage chemotaxis and neurite outgrowth. Collectively, our results indicate that CXCL12 is a brown adipocyte-enriched, cold-induced secreted factor involved in adipocyte function and the BAT microenvironment communication network.http://www.sciencedirect.com/science/article/pii/S2212877825000092Brown adipocyteSecretomeCXCL12Cold acclimationIntercellular communication |
| spellingShingle | Marina Agueda-Oyarzabal Marie S. Isidor Kaja Plucińska Lars R. Ingerslev Oksana Dmytriyeva Patricia S.S. Petersen Sara Laftih Axel B. Pontoppidan Jo B. Henningsen Kaja Rupar Erin L. Brown Thue W. Schwartz Romain Barrès Zachary Gerhart-Hines Camilla C. Schéele Brice Emanuelli Transcriptomic signatures of cold acclimated adipocytes reveal CXCL12 as a Brown autocrine and paracrine chemokine Molecular Metabolism Brown adipocyte Secretome CXCL12 Cold acclimation Intercellular communication |
| title | Transcriptomic signatures of cold acclimated adipocytes reveal CXCL12 as a Brown autocrine and paracrine chemokine |
| title_full | Transcriptomic signatures of cold acclimated adipocytes reveal CXCL12 as a Brown autocrine and paracrine chemokine |
| title_fullStr | Transcriptomic signatures of cold acclimated adipocytes reveal CXCL12 as a Brown autocrine and paracrine chemokine |
| title_full_unstemmed | Transcriptomic signatures of cold acclimated adipocytes reveal CXCL12 as a Brown autocrine and paracrine chemokine |
| title_short | Transcriptomic signatures of cold acclimated adipocytes reveal CXCL12 as a Brown autocrine and paracrine chemokine |
| title_sort | transcriptomic signatures of cold acclimated adipocytes reveal cxcl12 as a brown autocrine and paracrine chemokine |
| topic | Brown adipocyte Secretome CXCL12 Cold acclimation Intercellular communication |
| url | http://www.sciencedirect.com/science/article/pii/S2212877825000092 |
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