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Primary cilia are dysfunctional in obese adipose-derived mesenchymal stem cells
20 September 2018 (online)
Maternal obesity is linked to gestational diseases like preeclampsia (PE). Adipose-derived mesenchymal stem cells (ASCs) are fundamental in the surveillance of adipose tissue and become impaired in obesity. We hypothesized that dysfunctional ASCs could promote the development of obesity and its related diseases like PE. In this study we have addressed if the primary cilium, a sensory organelle that protrudes from the cell surface, is impaired and if this affects the functions of ASCs in obesity.
ASCs were isolated from adipose tissues of lean (12) and obese (10) donors for this study. Multiple methods including indirect immunofluorescence staining, immunohistochemistry, Western blot analysis, gene analysis, living cell microscopy and migration assay were performed to investigate the cellular functions as well as pathways of the primary cilium in ASCs.
ASCs from obese individuals have defective primary cilia, which are shortened and unable to properly respond to stimuli. Impaired cilia compromise ASC functionalities such as migration and differentiation. Exposure to obesity related hypoxia and cytokines shortens cilia of lean ASCs. Like obese ASCs, lean ASCs treated with IL6 are deficient in the Hedgehog pathway. Obese ASCs express increased levels of ciliary disassembly regulator genes like AURKA.
Our results highlight that obesity related factors impair the primary cilium of ASCs. This event renders ASCs dysfunctional, resulting in diseased adipose tissue. Impaired cilia in ASCs may be a key event in the pathogenesis of obesity and its associated diseases.