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

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% VO(2max). 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 glucose(AUC), insulin(AUC), and insulin resistance index in individuals with obesity. Consistent with this improvement in insulin sensitivity, we observed that Fet‐A(AUC), pFet‐A(AUC), 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‐A(AUC) 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://clinicaltrials.gov/ct2/show/NCT03478046.