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.
