post_excerpt; ?>

Primary Cilia Are Dysfunctional in Obese Adipose-Derived Mesenchymal Stem Cells.

Aim:

Obesity is associated with a variety of disorders including cardiovascular diseases, diabetes mellitus and
cancer. 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. In this study we have addressed if the primary cilium, a
sensory organelle that protrudes from the cell surface, is impaired in ASCs of obese patients. The primary
cilium is known to be crucial for maintaining stemness, defining the cell phenotype, and functioning as a
signal sensor and transducer in stem/progenitor cells. Therefore, a damaged primary cilium could affect
the functions of ASCs on multiple levels to fuel the further development of obesity related diseases.

Materials & Methods:

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 differentiation assays were performed to investigate the cellular
functions as well as pathways of the primary cilium in ASCs.

Results:

ASCs from obese individuals have defective primary cilia, which are shortened and unable to properly
respond or transduce 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. Moreover, low dose of Aurora A or HDAC6
inhibitors rescue the phenotype and function of obese primary cilia.

Summary:

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 rescue might provide an alternative strategy for combating obesity and its
associated diseases.