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

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://clinicaltrials.gov/ct2/show/NCT03478046.