The influence of IMPDH activity on ciliogenesis and adipogenesis of 3T3-L1 cells while undergoing differentiation

Abstract

The functional roles of primary cilia and inosine 5′-monophosphate dehydrogenase (IMPDH) are among the hot topics in today's adipogenesis research. Considering the reported interaction between IMPDH and ADP Ribosylation Factor-Like GTPase 13B (ARL13B), as a key ciliary protein, our study focused on this interaction during the ciliogenesis process while 3T3-L1 pre-adipocytes undergoing differentiation to lipid-accumulating adipocytes. Our results indicated that, in the early days of differentiation, when cilium length is long, IMPDH expression is high and its interaction with ARL13B is low. Conversely, in the last days of differentiation, the cilia length and IMPDH expression reduced while, the IMPDH/ARL13B interaction remains high relative to the initial days. In either of these two situations, IMPDH was not documented within the cilia. The extent of the interaction between IMPDH and ARL13B might account for the lack of co-localization of IMPDH and ARL13B within cilia during the process of differentiation. Although, inhibiting IMPDH in the early days of differentiation did not have a significant effect on cilia length, it did reduce adipogenesis by limiting mitotic clonal expansion through arresting cells in the G1/G0 phase. These findings provide the ground for further research to investigate the relationship between the IMPDH/ARL13B interaction and cilia length, which decline in obesity.