Study of Changes in Skeletal Muscle After Caloric Restriction

Diacylglycerols and Insulin Action in Skeletal Muscle Upon Caloric Restriction

Research has shown that fat stored within muscles affects the muscle's sensitivity to insulin and ability to handle blood glucose. The purpose of this study is to examine the effects of weight loss surgery-induced caloric restriction on the accumulation and types of fats within skeletal muscle, as well as the effects of such caloric restriction on insulin sensitivity and inflammatory responses in skeletal muscle. The investigator proposes that caloric restriction will result in decreases in diacylglycerols enriched with saturated fat and increases in diacylglycerols enriched with monounsaturated fats.

Study Overview

• Status: Active, not recruiting
• Conditions: Obesity

Detailed Description

We hypothesize that in a setting of surgically-induced weight loss decrements in select DAGs result in improved glucose utilization, altered insulin signaling and decreased inflammatory responses. We propose to examine the impact of molecular DAG species accumulation on glucose utilization, insulin signaling and inflammation in skeletal muscle from morbidly obese subjects before/after 10% weight loss facilitated by Roux-en-Y Gastric Bypass (RYGB). We will compare these results to those from a control, normal weight cohort

The detected differences in DAG molecular species, insulin action, inflammatory responses between normal and obese subjects (before/after weight loss) will emphasize pathways coordinately altered as a consequence of adiposity and RYGB surgery. The primary endpoints for this study will be: Insulin sensitivity (glucose Rd, insulin levels, DAG mass, DAG species amounts).Secondary endpoints will be: FFA levels, inflammatory cytokine production, and insulin signaling in skeletal muscle.

• Study Type: Observational
• Enrollment (Estimated): 24

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Female subjects approved for Roux-en-Y gastric bypass surgery at Vanderbilt University Medical Center.

Description

Inclusion Criteria:

• For Normal Weight Subjects:

  • Age 21-65 years
  • BMI of 21 to 27 kg/m2
  • Normal glucose tolerance as determined by OGTT on day of screening
  • No family history of diabetes

• For Morbidly Obese Subjects:

  • Age 21-65 years
  • BMI of 30 to 65 kg/m2
  • Scheduled for Roux-en-Y gastric bypass at Vanderbilt Medical Center
  • Insulin resistant as determined by OGTT on day of screening

Exclusion Criteria (for all subjects):

• Clinically significant heart disease
• Clinically significant hepatic or renal disease
• Pregnancy
• Breastfeeding
• Any abnormality that would preclude safe completion of study
• Use of statins
• Use of thiazide or furosemide diuretics, beta blockers, or other chronic medications with known adverse effects on glucose tolerance levels unless subject has been on stable dose of such medications for the past 3 months before entering the study

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Normal body weight; Female subjects, ages 21-65 yrs, with BMI of 21-27 kg/m2 with normal glucose tolerance.
Roux-en-Y gastric bypass; Female subjects ages 21-65 with insulin resistance and scheduled for Roux-en-Y gastric bypass at Vanderbilt University Medical Center will be studied before and 4-6 weeks after surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
UPLC-ESI MS/MS profiling of lipd extracts from muscle biopsies to evaluate effects of gastric bypass induced-caloric restriction on diacylglycerol molecular species accumulation.	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
To evaluate the effects of gastric bypass induced-caloric restriction on skeletal muscle insulin action via a hyperinsulinemic-euglycemic clamp and profiling markers of insulin signaling.	1 year
To evaluate the effects of gastric bypass induced-caloric restriction on lipid-mediated inflammatory responses by profiling cytokines and free fatty acids in blood and inflammation markers in skeletal muscle biopsies.	1 year

Collaborators and Investigators

• Sponsor: Vanderbilt University
• Investigators: Principal Investigator: Charles R Flynn, PhD, Vanderbilt University Medical Center; Study Chair: Naji Abumrad, MD, Vanderbilt University Medical Center

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): November 1, 2013
• Study Completion (Estimated): November 1, 2026

Study Registration Dates

• First Submitted: October 7, 2009
• First Submitted That Met QC Criteria: October 8, 2009
• First Posted (Estimated): October 12, 2009

Study Record Updates

• Last Update Posted (Actual): July 8, 2025
• Last Update Submitted That Met QC Criteria: July 2, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Inflammation; Obesity; Insulin sensitivity
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Overweight; Obesity
• Other Study ID Numbers: IRB #091145