Nck1 Deficiency Impairs Adipogenesis by Activation of PDGFRα in Preadipocytes
Summary: Obesity results from an excessive expansion of white adipose tissue (WAT), which is still poorly understood from an etiologic-mechanistic perspective. Here, we report that Nck1, a Src homology domain-containing adaptor, is upregulated during WAT expansion and in vitro adipogenesis. In agree...
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| Format: | Article |
| Language: | English |
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Elsevier
2018-08-01
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| Series: | iScience |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004218300981 |
| _version_ | 1811212745824010240 |
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| author | Nida Haider Julie Dusseault Louise Larose |
| author_facet | Nida Haider Julie Dusseault Louise Larose |
| author_sort | Nida Haider |
| collection | DOAJ |
| description | Summary: Obesity results from an excessive expansion of white adipose tissue (WAT), which is still poorly understood from an etiologic-mechanistic perspective. Here, we report that Nck1, a Src homology domain-containing adaptor, is upregulated during WAT expansion and in vitro adipogenesis. In agreement, Nck1 mRNA correlates positively with peroxisome proliferator-activated receptor (PPAR) γ and adiponectin mRNAs in the WAT of obese humans, whereas Nck1-deficient mice display smaller WAT depots with reduced number of adipocyte precursors and accumulation of extracellular matrix. Furthermore, silencing Nck1 in 3T3-L1 preadipocytes increases the proliferation and expression of genes encoding collagen, whereas it decreases the expression of adipogenic markers and impairs adipogenesis. Silencing Nck1 in 3T3-L1 preadipocytes also promotes the expression of platelet-derived growth factor (PDGF)-A and platelet-derived growth factor receptor (PDGFR) α activation and signaling. Preventing PDGFRα activation using imatinib, or through PDGF-A or PDGFRα deficiency, inhibits collagen expression in Nck1-deficient preadipocytes. Finally, imatinib rescues differentiation of Nck1-deficient preadipocytes. Altogether, our findings reveal that Nck1 modulates WAT development through PDGFRα-dependent remodeling of preadipocytes. : Functional Aspects of Cell Biology; Pathophysiology Subject Areas: Functional Aspects of Cell Biology, Pathophysiology |
| first_indexed | 2024-04-12T05:34:27Z |
| format | Article |
| id | doaj.art-5c0ac1cf610443d7be079ee471a8c253 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-12T05:34:27Z |
| publishDate | 2018-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-5c0ac1cf610443d7be079ee471a8c2532022-12-22T03:45:55ZengElsevieriScience2589-00422018-08-0162237Nck1 Deficiency Impairs Adipogenesis by Activation of PDGFRα in PreadipocytesNida Haider0Julie Dusseault1Louise Larose2Division of Experimental Medicine, Department of Medicine, McGill University and The Research Institute of McGill University Health Centre, Glen Site, Bloc E, Rm E02-7244, 1001 Decarie Boulevard, Montreal, QC H4A 3J1 CanadaDivision of Experimental Medicine, Department of Medicine, McGill University and The Research Institute of McGill University Health Centre, Glen Site, Bloc E, Rm E02-7244, 1001 Decarie Boulevard, Montreal, QC H4A 3J1 CanadaDivision of Experimental Medicine, Department of Medicine, McGill University and The Research Institute of McGill University Health Centre, Glen Site, Bloc E, Rm E02-7244, 1001 Decarie Boulevard, Montreal, QC H4A 3J1 Canada; Corresponding authorSummary: Obesity results from an excessive expansion of white adipose tissue (WAT), which is still poorly understood from an etiologic-mechanistic perspective. Here, we report that Nck1, a Src homology domain-containing adaptor, is upregulated during WAT expansion and in vitro adipogenesis. In agreement, Nck1 mRNA correlates positively with peroxisome proliferator-activated receptor (PPAR) γ and adiponectin mRNAs in the WAT of obese humans, whereas Nck1-deficient mice display smaller WAT depots with reduced number of adipocyte precursors and accumulation of extracellular matrix. Furthermore, silencing Nck1 in 3T3-L1 preadipocytes increases the proliferation and expression of genes encoding collagen, whereas it decreases the expression of adipogenic markers and impairs adipogenesis. Silencing Nck1 in 3T3-L1 preadipocytes also promotes the expression of platelet-derived growth factor (PDGF)-A and platelet-derived growth factor receptor (PDGFR) α activation and signaling. Preventing PDGFRα activation using imatinib, or through PDGF-A or PDGFRα deficiency, inhibits collagen expression in Nck1-deficient preadipocytes. Finally, imatinib rescues differentiation of Nck1-deficient preadipocytes. Altogether, our findings reveal that Nck1 modulates WAT development through PDGFRα-dependent remodeling of preadipocytes. : Functional Aspects of Cell Biology; Pathophysiology Subject Areas: Functional Aspects of Cell Biology, Pathophysiologyhttp://www.sciencedirect.com/science/article/pii/S2589004218300981 |
| spellingShingle | Nida Haider Julie Dusseault Louise Larose Nck1 Deficiency Impairs Adipogenesis by Activation of PDGFRα in Preadipocytes iScience |
| title | Nck1 Deficiency Impairs Adipogenesis by Activation of PDGFRα in Preadipocytes |
| title_full | Nck1 Deficiency Impairs Adipogenesis by Activation of PDGFRα in Preadipocytes |
| title_fullStr | Nck1 Deficiency Impairs Adipogenesis by Activation of PDGFRα in Preadipocytes |
| title_full_unstemmed | Nck1 Deficiency Impairs Adipogenesis by Activation of PDGFRα in Preadipocytes |
| title_short | Nck1 Deficiency Impairs Adipogenesis by Activation of PDGFRα in Preadipocytes |
| title_sort | nck1 deficiency impairs adipogenesis by activation of pdgfrα in preadipocytes |
| url | http://www.sciencedirect.com/science/article/pii/S2589004218300981 |
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