Abstract
Background: Fetuin-A is a hepatokine linked to the development of insulin resistance. The purpose of this study was to determine if 60 days head-down-tilt (HDT) bed rest increased circulating fetuin-A and if it was linked to whole body insulin sensitivity (IS). Additionally, we examined whether reactive jump training (RJT) could alleviate the metabolic changes associated with bed rest.Methods: 23 young men (29 ± 6 years, 181 ± 6 cm, 77 ± 7 kg) were randomized to a control (CTRL, n = 11) or RJT group (JUMP, n = 12) and exposed to 60 days of bed rest. Before and after bed rest, body composition and were measured and an oral glucose tolerance test was performed to estimate IS. Circulating lipids and fetuin-A were measured in fasting serum.Results: Body weight, lean mass, and decreased in both groups following bed rest, with greater reductions in CTRL (p < 0.05). There was a main effect of time, but not the RJT intervention, for the increase in fetuin-A, triglycerides (TG), area under the curve for glucose (AUCG) and insulin (AUCI), and the decrease in Matsuda and tissue-specific IS (p < 0.05). Fetuin-A increased in participants who became less insulin sensitive (p = 0.019). In this subgroup, liver IS and adipose IS decreased (p < 0.05), while muscle IS was unchanged. In a subgroup, where IS did not decrease, fetuin-A did not change. Liver IS increased (p = 0.012), while muscle and adipose tissue IS remained unchanged.Conclusions: In this study, we report an increase in circulating fetuin-A following 60 days of bed rest, concomitant with reduced IS, which could not be mitigated by RJT. The amount of fetuin-A released from the liver may be an important determinant of changes in whole body IS. In this regard, it may also be a useful biomarker of individual variation due to inactivity or lifestyle interventions.
Highlights
Physical inactivity and exposure to microgravity induce aginglike phenotypic changes that are associated with the etiology of many chronic diseases (Bergouignan et al, 2011; Hart and Zernicke, 2020)
The purpose of this study was to determine if 60 days of extreme physical inactivity increased circulating fetuin-A and if those changes correlated with whole body insulin sensitivity
We examined whether reactive jump training (RJT), a countermeasure used to maintain skeletal muscle mass, was able to attenuate the deterioration in metabolic health that occurs with prolonged inactivity
Summary
Physical inactivity and exposure to microgravity induce aginglike phenotypic changes that are associated with the etiology of many chronic diseases (Bergouignan et al, 2011; Hart and Zernicke, 2020). Insulin resistance is a multi-faceted disruption of the action of insulin in skeletal muscle, adipose tissue, vasculature, brain, and the liver, leading to hyperinsulinemia and reduced glucose disposal (Cox-York and Pereira, 2020). It is associated with impaired oxidative capacity, increased circulating and deposition of lipids, and metabolic inflexibility. These whole body and cellular changes have been observed following bed rest studies, even when energy balance is maintained (Bergouignan et al, 2006, 2009, 2011; Kenny et al, 2017; Rudwill et al, 2018). We examined whether reactive jump training (RJT) could alleviate the metabolic changes associated with bed rest
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