Characterization of subcutaneous and visceral de-differentiated fat cells
Objective: The capacity of mature adipocytes to de-differentiate into fibroblast-like cells has been demonstrated in vitro and a few, rather specific in vivo conditions. A detailed comparison between de-differentiated fat (DFAT) cells and adipose stem and progenitor cells (ASPCs) from different adip...
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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/S2212877825000122 |
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| author | Yan Li Houyu Zhang Carlos F. Ibáñez Meng Xie |
| author_facet | Yan Li Houyu Zhang Carlos F. Ibáñez Meng Xie |
| author_sort | Yan Li |
| collection | DOAJ |
| description | Objective: The capacity of mature adipocytes to de-differentiate into fibroblast-like cells has been demonstrated in vitro and a few, rather specific in vivo conditions. A detailed comparison between de-differentiated fat (DFAT) cells and adipose stem and progenitor cells (ASPCs) from different adipose depots is yet to be conducted. Moreover, whether de-differentiation of mature adipocytes from classical subcutaneous and visceral depots occurs under physiological conditions remains unknown. Methods: Here, we used in vitro ''ceiling culture'', single cell/nucleus RNA sequencing, epigenetic anaysis and genetic lineage tracing to address these unknowns. Results: We show that in vitro-derived DFAT cells have lower adipogenic potential and distinct cellular composition compared to ASPCs. In addition, DFAT cells derived from adipocytes of inguinal origin have dramatically higher adipogenic potential than DFAT cells of the epididymal origin, due in part to enhanced NF-KB signaling in the former. We also show that high-fat diet (HFD) feeding enhances DFAT cell colony formation and re-differentiation into adipocytes, while switching from HFD to chow diet (CD) only reverses their re-differentiation. Moreover, HFD deposits epigenetic changes in DFAT cells and ASPCs that are not reversed after returning to CD. Finally, combining genetic lineage tracing and single cell/nucleus RNA sequencing, we demonstrate the existence of DFAT cells in inguinal and epididymal adipose depots in vivo, with transcriptomes resembling late-stage ASPCs. Conclusions: These data uncover the cell type- and depot-specific properties of DFAT cells, as well as their plasticity in response to dietary intervention. This knowledge may shed light on their role in life style change-induced weight loss and regain. |
| format | Article |
| id | doaj-art-581d2cda8e4c44d9b3b144dd1ee1d03d |
| institution | Kabale University |
| issn | 2212-8778 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Metabolism |
| spelling | doaj-art-581d2cda8e4c44d9b3b144dd1ee1d03d2025-02-07T04:47:30ZengElsevierMolecular Metabolism2212-87782025-03-0193102105Characterization of subcutaneous and visceral de-differentiated fat cellsYan Li0Houyu Zhang1Carlos F. Ibáñez2Meng Xie3Chinese Institute for Brain Research, Zhongguancun Life Science Park, Beijing 102206, China; Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, ChinaChinese Institute for Brain Research, Zhongguancun Life Science Park, Beijing 102206, China; Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, ChinaChinese Institute for Brain Research, Zhongguancun Life Science Park, Beijing 102206, China; School of Life Sciences, Peking University, Beijing 100871, China; Peking-Tsinghua Center for Life Sciences, Beijing 100871, China; PKU-IDG/McGovern Institute for Brain Research, Beijing 100871, China; Department of Neuroscience, Karolinska Institute, Stockholm 17165, Sweden; Corresponding author. Lui Che Woo Building, Peking University, Beijing 102206, China.Peking-Tsinghua Center for Life Sciences, Beijing 100871, China; PKU-IDG/McGovern Institute for Brain Research, Beijing 100871, China; School of Psychological and Cognitive Sciences, Peking University, Beijing 100871, China; Beijing Key Laboratory of Behavior and Mental Health, Beijing 100871, China; Biosciences and Nutrition Unit, Department of Medicine Huddinge, Karolinska Institute, Huddinge 14183, Sweden; Corresponding author. Lui Che Woo Building, Peking University, Beijing 102206, China.Objective: The capacity of mature adipocytes to de-differentiate into fibroblast-like cells has been demonstrated in vitro and a few, rather specific in vivo conditions. A detailed comparison between de-differentiated fat (DFAT) cells and adipose stem and progenitor cells (ASPCs) from different adipose depots is yet to be conducted. Moreover, whether de-differentiation of mature adipocytes from classical subcutaneous and visceral depots occurs under physiological conditions remains unknown. Methods: Here, we used in vitro ''ceiling culture'', single cell/nucleus RNA sequencing, epigenetic anaysis and genetic lineage tracing to address these unknowns. Results: We show that in vitro-derived DFAT cells have lower adipogenic potential and distinct cellular composition compared to ASPCs. In addition, DFAT cells derived from adipocytes of inguinal origin have dramatically higher adipogenic potential than DFAT cells of the epididymal origin, due in part to enhanced NF-KB signaling in the former. We also show that high-fat diet (HFD) feeding enhances DFAT cell colony formation and re-differentiation into adipocytes, while switching from HFD to chow diet (CD) only reverses their re-differentiation. Moreover, HFD deposits epigenetic changes in DFAT cells and ASPCs that are not reversed after returning to CD. Finally, combining genetic lineage tracing and single cell/nucleus RNA sequencing, we demonstrate the existence of DFAT cells in inguinal and epididymal adipose depots in vivo, with transcriptomes resembling late-stage ASPCs. Conclusions: These data uncover the cell type- and depot-specific properties of DFAT cells, as well as their plasticity in response to dietary intervention. This knowledge may shed light on their role in life style change-induced weight loss and regain.http://www.sciencedirect.com/science/article/pii/S2212877825000122Adipocyte de-differentiationDFAT cell re-differentiationNF-κBDiet interventionscRNA-seq/snRNA-seqDNA methylation |
| spellingShingle | Yan Li Houyu Zhang Carlos F. Ibáñez Meng Xie Characterization of subcutaneous and visceral de-differentiated fat cells Molecular Metabolism Adipocyte de-differentiation DFAT cell re-differentiation NF-κB Diet intervention scRNA-seq/snRNA-seq DNA methylation |
| title | Characterization of subcutaneous and visceral de-differentiated fat cells |
| title_full | Characterization of subcutaneous and visceral de-differentiated fat cells |
| title_fullStr | Characterization of subcutaneous and visceral de-differentiated fat cells |
| title_full_unstemmed | Characterization of subcutaneous and visceral de-differentiated fat cells |
| title_short | Characterization of subcutaneous and visceral de-differentiated fat cells |
| title_sort | characterization of subcutaneous and visceral de differentiated fat cells |
| topic | Adipocyte de-differentiation DFAT cell re-differentiation NF-κB Diet intervention scRNA-seq/snRNA-seq DNA methylation |
| url | http://www.sciencedirect.com/science/article/pii/S2212877825000122 |
| work_keys_str_mv | AT yanli characterizationofsubcutaneousandvisceraldedifferentiatedfatcells AT houyuzhang characterizationofsubcutaneousandvisceraldedifferentiatedfatcells AT carlosfibanez characterizationofsubcutaneousandvisceraldedifferentiatedfatcells AT mengxie characterizationofsubcutaneousandvisceraldedifferentiatedfatcells |