['Although decreased levels of circulating TRAIL have been associated to cardiovascular risk and overall mortality, the mechanisms controlling TRAIL levels in physiopathological conditions are currently unknown. The aim of the present study was to investigate whether changes in the energy intake and insulin sensitivity may influence circulating TRAIL, and to analyze potential relationships between circulating TRAIL and changes in fat mass in healthy subjects receiving hypocaloric or hypercaloric diets.', 'Three distinct groups of participants were studied, at the end of a 14-day (n\xa0=\xa09), 35-day (n\xa0=\xa030) or 60-day (n\xa0=\xa016) period of experimental bed rest to induce insulin resistance and during controlled ambulation, after receiving eucaloric, hypocaloric or hypercaloric diets.', 'After bed rest conditions, energy restriction significantly decreased circulating TRAIL, while overfeeding significantly increased TRAIL levels with respect to eucaloric control subjects. Moreover, a positive correlation was found between levels of circulating TRAIL and energy intake as well as between circulating TRAIL and energy balance, as determined by changes in fat mass in these subjects.'] Does the energy balance positively regulate the levels of circulating TNF-related apoptosis inducing ligand in humans?