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

Study Overview
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Brief Summary
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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.

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

Conditions
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Obesity, Insulin Sensitivity, Muscle Weakness, Adiposity, Insulin Resistance

Intervention / Treatment
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* Behavioral: Diet Weight Loss


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Generally healthy men and women aged 18-70 BMI between 30-40 Less than 1 hour of exercise per week Women: 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: Currently going through menopause or peri-menopause Pregnant or breastfeeding History of Polycystic Ovary Syndrome

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Diet Weight Loss<br>Low calorie meal replacement shakes | Behavioral: Diet Weight Loss<br>* Low calorie diet of meal replacement shakes<br>|
| No Intervention: Delayed Intervention<br>Normal feeding | |

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IMAT, Intermuscular Adipose Tissue, Weight Loss, Diet