AUTHOR=Ward Kiera , Mulder Edwin , Frings-Meuthen Petra , O’Gorman Donal J. , Cooper Diane 

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

JOURNAL=Frontiers in Physiology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2020.573581

DOI=10.3389/fphys.2020.573581

ISSN=1664-042X

ABSTRACT=<p><bold>Background</bold>: 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.</p><p><bold>Methods</bold>: 23 young men (29 ± 6 years, 181 ± 6 cm, 77 ± 7 kg) were randomized to a control (CTRL, <italic>n</italic> = 11) or RJT group (JUMP, <italic>n</italic> = 12) and exposed to 60 days of bed rest. Before and after bed rest, body composition and <inline-formula><mml:math id="M1" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mover accent="true"><mml:mtext>V</mml:mtext><mml:mo>.</mml:mo></mml:mover><mml:mtext>O</mml:mtext><mml:msub><mml:mtext></mml:mtext><mml:mrow><mml:mn>2</mml:mn><mml:mo>⁢</mml:mo><mml:mtext>p</mml:mtext><mml:mo>⁢</mml:mo><mml:mtext>e</mml:mtext><mml:mo>⁢</mml:mo><mml:mtext>a</mml:mtext><mml:mo>⁢</mml:mo><mml:mtext>k</mml:mtext></mml:mrow></mml:msub></mml:mrow></mml:math></inline-formula> were measured and an oral glucose tolerance test was performed to estimate IS. Circulating lipids and fetuin-A were measured in fasting serum.</p><p><bold>Results</bold>: Body weight, lean mass, and <inline-formula><mml:math id="M2" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mover accent="true"><mml:mtext>V</mml:mtext><mml:mo>.</mml:mo></mml:mover><mml:mtext>O</mml:mtext><mml:msub><mml:mtext></mml:mtext><mml:mrow><mml:mn>2</mml:mn><mml:mo>⁢</mml:mo><mml:mtext>p</mml:mtext><mml:mo>⁢</mml:mo><mml:mtext>e</mml:mtext><mml:mo>⁢</mml:mo><mml:mtext>a</mml:mtext><mml:mo>⁢</mml:mo><mml:mtext>k</mml:mtext></mml:mrow></mml:msub></mml:mrow></mml:math></inline-formula> decreased in both groups following bed rest, with greater reductions in CTRL (<italic>p</italic> &lt; 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 (<italic>p</italic> &lt; 0.05). Fetuin-A increased in participants who became less insulin sensitive (<italic>p</italic> = 0.019). In this subgroup, liver IS and adipose IS decreased (<italic>p</italic> &lt; 0.05), while muscle IS was unchanged. In a subgroup, where IS did not decrease, fetuin-A did not change. Liver IS increased (<italic>p</italic> = 0.012), while muscle and adipose tissue IS remained unchanged.</p><p><bold>Conclusions</bold>: 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.</p>