Fetuin-A as a Potential Biomarker of Metabolic Variability Following 60 Days of Bed Rest

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 V. O 2peak 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 V. O 2peak 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.

Muscle atrophy phenotype gene expression during spaceflight is linked to a metabolic crosstalk in both the liver and the muscle in mice

“…Interestingly, increased concentration of Fetuin-A showed to have the inverse effect of the previously described hepatokines ( Jensen-Cody and Potthoff, 2021 ; Seo et al., 2021 ). The levels of Fetuin-A increase after 60 day of bed rest, a ground model for microgravity effects, and we found in the literature a positive correlation between the Fetuin-A levels and the gene expression of Serpina6 and Rdh7, two genes we identified in our gene cluster ( Herrmann et al., 2020 ; Thakur et al., 2008 ; Ward et al., 2020 ). Interestingly, Fetuin-A, as well as FGF21 and ANGPTL4 genes are among the correlating genes in the liver of mice during spaceflight reported by the liver versus quadriceps sPLS-DA.…”

Physiology of physical inactivity, sedentary behaviours and non‐exercise activity: insights from the space bedrest model

“…In all these studies, the resistance exercise session was performed as a single continuous bout; however novel data suggest that spreading activity throughout the day as multiple short active bouts may have more potent health-enhancing effects (Loh et al, 2019). Nevertheless, when exercise was performed as intermittent, frequent jumping squats spread throughout the day muscle mass loss was prevented, but not the reduction in whole-body and peripheral insulin sensitivity (Ward et al, 2020).…”

“…Nevertheless, when exercise was performed as intermittent, frequent jumping squats spread throughout the day, muscle mass loss was prevented, but not the reduction in whole‐body and peripheral insulin sensitivity (Ward et al . 2020). Taken together, the low energy expenditure associated with resistance exercise (Table 1) may be responsible for partial or limited protective effects on metabolic health outcomes.…”

Effects of long‐term simulated microgravity on liver metabolism in rhesus macaques

“…81,82 However, the body weight loss of monkeys with 42-day HDBR was around 30%, much higher than that of humans with 60-day HDBR (less than 5%) or mice with 28-day hindlimb unloading (less than 10%). 19,52,83 It suggests that stress is a non-negligible factor in the monkey model of HDBR. Considering the impact of glucocorticoids on lipid deposition in the liver, 79 the alterations in plasma and liver of HDBR monkeys are likely the combined effects of simulated microgravity and stress.…”