Nck1 Deficiency Impairs Adipogenesis by Activation of PDGFR? in Preadipocytes.
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ABSTRACT: 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) ? 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) ? activation and signaling. Preventing PDGFR? activation using imatinib, or through PDGF-A or PDGFR? 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 PDGFR?-dependent remodeling of preadipocytes.
SUBMITTER: Haider N
PROVIDER: S-EPMC6137712 | biostudies-literature | 2018 Aug
REPOSITORIES: biostudies-literature
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