Serum fetuin-A and Ser312 phosphorylated fetuin-A responses and markers of insulin sensitivity after a single bout of moderate intensity exercise

Guang Ren, Robert L Bowers, Teayoun Kim, Alonzo J Mahurin, Peter W Grandjean, Suresh T Mathews, Guang Ren, Robert L Bowers, Teayoun Kim, Alonzo J Mahurin, Peter W Grandjean, Suresh T Mathews

Abstract

Fetuin-A (Fet-A), secreted by the liver and adipose tissue, inhibits insulin receptor tyrosine kinase activity and modulates insulin action. Numerous studies have shown association of elevated serum Fet-A concentrations with obesity, non-alcoholic fatty liver disease, and type 2 diabetes. Both moderate body weight loss (5%-10%) and significant body weight loss have been shown to decrease serum Fet-A and improve insulin sensitivity. Currently, there are no studies examining the effects of a single bout of exercise on serum Fet-A or Ser312-pFet-A (pFet-A) responses. We hypothesized that a single bout of moderate-intensity exercise will lower serum Fet-A and that these changes will be associated with an improvement in insulin sensitivity. Thirty-one individuals with obesity and 11 individuals with normal body weight were recruited. Participants underwent a single bout of treadmill walking, expending 500 kcal at 60%-70% VO2max . Oral glucose tolerance tests (OGTT) were administered before the single bout of exercise (Pre Ex) and 24 h after exercise (24h Post Ex). In individuals with obesity, we observed a transient elevation of serum Fet-A concentrations, but not pFet-A, immediately after exercise (Post Ex). Further, a single bout of exercise decreased glucoseAUC , insulinAUC , and insulin resistance index in individuals with obesity. Consistent with this improvement in insulin sensitivity, we observed that Fet-AAUC , pFet-AAUC , 2 h pFet-A, and 2 h pFet-A/Fet-A were significantly lower following a single bout of exercise. Further, reductions in serum Fet-AAUC 24h Post Ex were correlated with a reduction in insulin resistance index. Together, this suggests that alterations in serum Fet-A following a single bout of moderate-intensity endurance exercise may play a role in the improvement of insulin sensitivity. CLINICAL TRIAL REGISTRATION: NCT03478046; https://ichgcp.net/clinical-trials-registry/NCT03478046.

Keywords: fetuin-A; insulin sensitivity; obesity; phosphofetuin-A; single bout exercise.

Conflict of interest statement

The authors declared no conflicts of interest.

© 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.

Figures

FIGURE 1
FIGURE 1
Timeline for blood sampling and single bout of exercise. On day 3, an oral glucose tolerance test was administered. On day 7, participants completed a single bout of endurance exercise expending 500 kcal, 60%–70% VO2max. Fasting blood samples were obtained pre‐exercise (Pre Ex), post exercise (Post Ex), and 24 h after the single bout of exercise (24h Post Ex) to assess Fet‐A, pFet‐A, and markers of insulin sensitivity. An oral glucose tolerance test was administered 24h Post Ex to analyze area under the curve (AUC) for glucose, insulin, insulin resistance index, Fet‐A, and pFet‐A
FIGURE 2
FIGURE 2
Fasting serum Fet‐A, pFet‐A, pFet‐A/Fet‐A, and metabolic indices individuals with normal weight (n = 11) and individuals with obesity (n = 31) and all participants (n = 42) before exercise (Pre Ex), immediately after exercise (Post Ex), and 24 h after a single bout of exercise expending 500 kcal (24h Post Ex). A representative Western blot depicting alterations in serum pFet‐A, from Pre Ex, Post Ex, and 24h Post Ex timepoints in an individual with normal weight and an individual with obesity is shown (inset). NEFA: non‐esterified fatty acids; HOMA‐IR: Homeostasis model assessment of insulin resistance; Adipose‐IR: adipose insulin resistance; and QUICKI: Quantitative insulin sensitivity check index. Data are expressed as Mean ± SEM. Statistical significance for comparisons of all participants are shown as follows: ***Pre‐Ex vs Post Ex, p < 0.001; ###Post Ex vs 24h Post Ex, p < 0.001; #Post Ex vs 24 h Post Ex, p < 0.05. In individuals with normal weight or obesity, different letters in superscript following values indicate statistical significance, p < 0.05
FIGURE 3
FIGURE 3
Area under the curve (AUC) for glucose, insulin, Fet‐A and pFet‐A was calculated following an oral glucose tolerance test to compare changes (Δ) from Pre Ex to 24h Post Ex in serum Fet‐AAUC with Δ in glucoseAUC (a), insulinAUC (b), and insulin resistance index (insulinAUC × glucoseAUC/106) (c); Δ in pFetAAUC with Δ in glucoseAUC (d); insulinAUC (e); insulin resistance index (f); and Δ in pFet‐AAUC/Fet‐AAUC with Δ in glucoseAUC (g); insulinAUC (h); insulin resistance index (i) in all participants. Correlation was determined using Pearson product‐moment correlation coefficient (individuals with normal weight shown using open circles and individuals with obesity shown using closed circles)

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