Fetuin-A Phosphorylation Status in Insulin Resistance and Metabolic Syndrome

Alterations in Phosphorylated Fetuin-A, a Novel Regulator of Insulin Action in Insulin Resistance and Metabolic Syndrome: Effects of Lifestyle Modification

Fetuin-A has been identified as a novel physiological regulator of insulin action in vitro, in intact cells and in vivo in animals. Previous research has shown that circulating levels of fetuin-A were increased in animal models of insulin resistance and diabetes. Additionally, several human investigation studies demonstrate a correlation of fetuin-A levels with body mass index, insulin resistance, and a fatty liver. Recently, the investigators have elucidated the role of fetuin-A phosphorylation in the regulation of insulin action, demonstrating that phosphorylation is critical for the inhibitory activity of fetuin-A. The objectives of this study are twofold: (1) Quantitate phosphorylated fetuin-A levels in individuals with insulin resistance and metabolic syndrome, and (2) Investigate the effects of lifestyle modifications (acute or chronic exercise and dietary modifications) on fetuin-A phosphorylation and insulin sensitivity.

There are several objectives of this study: (1) Quantitate phosphorylated fetuin-A levels and the daily variation in these levels in individuals with insulin resistance and metabolic syndrome; (2) Investigate the short-term responses of fetuin-A phosphorylation and changes in insulin resistance that occur with a single session of aerobic exercise; (3) Characterize and compare the total and temporal changes in fetuin-A phosphorylation and insulin resistance that occur with an 8 to 10% weight loss induced by chronic exercise training and dietary modification, and; (4) Investigate the influence of weight loss on the short-term responses of fetuin-A phosphorylation and changes in insulin resistance that occur with a single session of aerobic exercise. Our hypothesis is that phosphofetuin-A levels are tightly correlated with insulin resistance and that lifestyle modifications will improve insulin sensitivity and decrease phosphorylated fetuin-A levels.

Apparently healthy, weight-stable, obese and physically inactive male volunteers will be recruited. Intervention is an 8 to 10% weight loss induced by chronic exercise training and dietary modification

Compare the total and temporal changes in fetuin-A phosphorylation and insulin resistance that occur with an 8 to 10% weight loss induced by chronic exercise training and dietary modification

Total fetuin-A and phosphorylated fetuin-A levels will be measured once every 4 weeks until participant achieves a targeted weight-loss goal of 8-10%. It is anticipated that most participants will achieve their weight-loss goal within 6-10 months.

Inclusion Criteria: 30 to 65 years of age obese (BMI > 30 kg⋅m2 or % fat > 30, and waist girth > 88 cm) weight stable over the previous 6 months Exclusion Criteria: smoker documented cardiovascular or metabolic disease currently taking medication to alter lipid or glucose metabolism practicing regular leisure physical activity over the previous 6 months engaged in strenuous vocational activity over the previous 6 months signs or symptoms of latent heart disease conditions that would preclude treadmill walking

Ren G, Bowers RL, Kim T, Mahurin AJ, Grandjean PW, Mathews ST. Serum fetuin-A and Ser312 phosphorylated fetuin-A responses and markers of insulin sensitivity after a single bout of moderate intensity exercise. Physiol Rep. 2021 Mar;9(5):e14773. doi: 10.14814/phy2.14773.