|Title||Studies in microgravity, simulated microgravity and gravity do not support a gravitostat.|
|Publication Type||Journal Article|
|Year of Publication||2020|
|Authors||Turner, RT, Branscum, AJ, Wong, CP, Iwaniec, UT, Morey-Holton, E|
|Keywords||Animals, Energy Metabolism, Female, Hindlimb Suspension, Male, Mice, Obesity, Osteocytes, Rats, Rats, Sprague-Dawley, Rats, Wistar, Space Flight, Weightlessness, Weightlessness Simulation|
The gravitostat is purported to function as a leptin-independent, osteocyte-dependent mechanism for regulation of energy balance. If correct, reduced activation of gravitostat signaling caused by prolonged sitting may contribute to obesity. The gravitostat concept is supported by reduced body mass in rodents following surgical implantation of weighted capsules. However, the procedure induces a confounding injury response. We, therefore, sought to confirm a gravitostat by decreasing (microgravity and simulated microgravity) or increasing (simulated gravity) weight using less invasive models (spaceflight, hindlimb unloading and centrifugation). We also evaluated changes in weight following non-surgical injury (radiation). Male rats (Wistar, Sprague-Dawley and Fischer 344) ranging in age from 5-12 weeks at launch and flown for 4-19 days in low Earth orbit exhibited slightly lower (4-day flight) or no difference (all other studies) in weight compared to ground controls. Rats subjected to inflight (1.0 G) or ground (1.04 G and 1.56 G) centrifugation during a 19-day mission did not differ in weight. In female rats (Fischer 344), spaceflight (14 days) did not alter ovariectomy-induced weight gain. Finally, hindlimb unloading resulted in weight loss in lean and obese mice. The aforementioned findings are inconsistent with outcomes predicted by a gravitostat namely increased mass during weightlessness and decreased mass when subjected to >1 G simulated gravity. Injury (dose-associated graded increases in radiation) mimicked the leptin-independent weight changes attributed to a gravitostat. Taken together, these findings do not support gravitostat regulation of energy balance and suggest injury/stress as an alternative mechanism for weight loss induced by weighted capsules.
|Alternate Journal||J Endocrinol|