Effect of Weight Loss on Intermuscular Adipose Tissue (IMAT) Signaling

The goal of this intervention study is to learn about how weight loss impacts molecular signaling of intermuscular adipose tissue (IMAT) in individuals with obesity. The main question it aims to answer is how inflammatory molecules secreted by IMAT promote muscle insulin resistance and inflammation, and how these same molecules are diminished after weight loss. Following screening visits involving body composition measures, blood testing, strength testing, and a thigh muscle biopsy, participants will go through a 12-week dietary intervention for weight loss. After 12 weeks, this will be followed by the same testing and biopsies that were completed before the intervention. Researchers will then compare outcomes of individuals who lost weight to individuals who did not lose weight.

Study Overview

• Status: Recruiting
• Conditions: Obesity; Muscle Weakness; Insulin Resistance; Adiposity; Insulin Sensitivity
• Intervention / Treatment: Behavioral: Diet Weight Loss

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Bryan Bergman, PhD; Phone Number: 3037243919; Email: bryan.bergman@cuanschutz.edu
• Study Contact Backup: Name: Sophia Bowen; Phone Number: 3037240487; Email: sophia.bowen@cuanschutz.edu

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado Anschutz
      • Contact: Bryan Bergman, PhD
      • Principal Investigator: Bryan Bergman, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Generally healthy men and women aged 18-70
• BMI between 30-40
• Less than 1 hour of exercise per week

• Women:

  1. may be pre or post menopausal

Exclusion Criteria:

• Type 1 or Type 2 diabetes
• Thyroid disease
• History of lung disease
• Active use of nicotine
• Severe plasma lipid disorders
• Taking hormone replacement drugs, blood thinners, or thiazoladinediones

• Women:

  1. Currently going through menopause or peri-menopause
  2. Pregnant or breastfeeding
  3. History of Polycystic Ovary Syndrome

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Diet Weight Loss; Low calorie meal replacement shakes	Behavioral: Diet Weight Loss; Low calorie diet of meal replacement shakes
No Intervention: Delayed Intervention; Normal feeding

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin Sensitivity	Participants will undergo a standard 3-hour hyperinsulinemic/euglycemic clamp with insulin infused at 80 mU/m2/min, and glucose clamped at 90 mg/dl with a variable dextrose infusion.	12 weeks
Body Weight	Participant weight will be measured using BodyTrace scales during the 12 week intervention.	12 weeks
IMAT Content	A multi-slice MRI will be used to quantify IMAT and muscle content in both legs with acquisition of ~20 axial images (10 mm thickness) with 10 mm spacing between images starting superior to the patella. IMAT content will be quantified using the well-validated Sirlin 6-echo method and normalized to muscle volume.	12 weeks
Muscle Mass	A multi-slice MRI will be used to quantify IMAT and muscle content in both legs with acquisition of ~20 axial images (10 mm thickness) with 10 mm spacing between images starting superior to the patella. Muscle volume will be quantified using standard methods with anatomical cross-sectional area evaluated in each T1 weighted, high resolution, gradient echo profile scan, and multiplied by the length of the muscle.	12 weeks
Muscle Strength	Participants will perform quadriceps muscle strength testing using an isokinetic dynamometer.	12 weeks

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Institutes of Health (NIH)

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2024
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): September 1, 2028

Study Registration Dates

• First Submitted: November 8, 2023
• First Submitted That Met QC Criteria: November 10, 2023
• First Posted (Actual): November 13, 2023

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Weight Loss; Diet; IMAT; Intermuscular Adipose Tissue
• Additional Relevant MeSH Terms: Neurologic Manifestations; Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Neuromuscular Manifestations; Pathologic Processes; Nutrition Disorders; Metabolic Diseases; Overnutrition; Body Weight; Body Weight Changes; Glucose Metabolism Disorders; Hyperinsulinism; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Weight Loss; Muscle Weakness; Insulin Resistance; Therapeutics; Diet, Food, and Nutrition; Physiological Phenomena; Nutritional Physiological Phenomena; Diet Therapy; Nutrition Therapy; Diet; Diet, Reducing
• Other Study ID Numbers: 23-0545; 1R01DK134706-01A1 (U.S. NIH Grant/Contract)

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