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.

Study Overview

• Status: Completed
• Conditions: Obesity; Metabolic Syndrome
• Intervention / Treatment: Other: Weight loss

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Auburn, Alabama, United States, 36849
      • Auburn University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Obese individuals; 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	Other: Weight loss; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total plasma fetuin-A and phosphorylated fetuin-A	Measure total fetuin-A and phosphorylated fetuin-A levels in plasma	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.

Collaborators and Investigators

• Sponsor: Auburn University
• Investigators: Principal Investigator: Suresh Mathews, PhD, Auburn University

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2007
• Primary Completion (Actual): May 31, 2015
• Study Completion (Actual): May 31, 2015

Study Registration Dates

• First Submitted: March 19, 2018
• First Submitted That Met QC Criteria: March 23, 2018
• First Posted (Actual): March 27, 2018

Study Record Updates

• Last Update Posted (Actual): March 27, 2018
• Last Update Submitted That Met QC Criteria: March 23, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Disease; Hyperinsulinism; Syndrome; Metabolic Syndrome; Insulin Resistance
• Other Study ID Numbers: 07-210-MR0710

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No