Lipid signalling in human immune response and bone remodelling under microgravity

Since the first Apollo mission in 1969, microgravity has been linked to many alterations of astronauts' physiology, among which immunosuppression, altered inflammation and bone loss represent relevant examples. In the past 40 years, extensive investigations have been conducted in order to characterize the molecular mechanisms driving the alterations caused by prolonged weightlessness on human health. However, almost all studies eluded the role played by bioactive lipids, a vastly heterogeneous class of endogenous molecules, which, under normal conditions, control immune and bone homeostasis. This is somewhat surprising, because it is widely accepted that pathological derangement of the production or signalling of these endogenous compounds leads to the onset and/or progression of numerous diseases. In particular, eicosanoids and endocannabinoids are known to play a role in immune responses and bone remodelling. Both classes represent the only lipids as yet investigated in Space, and are increasingly recognised as promising therapeutic candidates to combat different human disorders. This review summarizes evidence gathered in the past two decades on the changes in these two pivotal lipid signalling systems, through both simulated and authentic weightlessness (i.e., on board the International Space Station and in parabolic flights).