Endocrine Abstracts

Obestatin (Ob) is a peptide recently identified as a product of the ghrelin gene. It was claimed to bind to the orphan receptor GPR39, but this finding is still a matter of debate. Ob exerts peripheral effects, for example, it promotes cell survival and has antiapoptotic actions in different cell lines. In addition, Ob has central effects, such as inhibition of thirst, modulation of anxiety, sleep and mnemonic functions. Mnemonic processes involve neurogenesis; in particular, hippocampal neurogenesis, which is fundamental for learning, comprise proliferation and differentiation of progenitor cells. Interestingly, both acylated ghrelin and the synthetic peptidyl GH secretagogue hexarelin have been previously shown to stimulate proliferation of adult rat hippocampal progenitor cells (AHPs). In the present study, we investigated Ob effects on proliferation and apoptosis of AHPs and the underlying signaling pathways. Ob effects were assessed in AHPs cultured in the absence of growth factors, a condition which reduces cell survival and proliferation, and increases apoptosis. Cell survival was measured by MTT assay; cell proliferation by BrdU incorporation and apoptosis through caspase-3 activity and Bcl-2 expression. Western blot analysis was performed to determine Ob-induced activation of neuroprotective pathways. Ob was found to promote cell survival and proliferation and to protect against growth factor deprivation-induced apoptosis. Furthermore, Ob effects involved PI3K/Akt, ERK1/2, Wnt/β-catenin and mTOR, as demonstrated by both activation of these pathways and by use of specific inhibitors. These results indicate that Ob promotes survival and proliferation, and inhibits apoptosis of AHPs through activation of neuroprotective pathways. Moreover, they suggest a possible role of Ob in neuronal precursor cell protection and candidate Ob as potential therapeutic molecule in conditions such as hippocampal damage.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.