Molecular and Hormonal Responses to Diet-Induced Insulin Resistance

Study Overview
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Brief Summary
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This study determined the effect of 7 days of high-fat overfeeding on whole-body glycaemic control, glucose kinetics, skeletal muscle insulin signalling, and markers of skeletal muscle microvascular function in 15 healthy young individuals.

Detailed Description
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Fifteen healthy, young individuals underwent metabolic testing before and after 7 days of high-fat overfeeding. We determined whole-body glycaemic control, glucose kinetics, skeletal muscle insulin signalling, and markers of skeletal muscle microvascular function. Stable isotope tracers were used to assess the rate of appearance of glucose from the gut, liver glucose output and whole-body glucose disposal. Insulin signalling was determined by Western blotting of skeletal muscle tissue. Microvascular function was assessed through the use of quantitative immunofluorescence microscopy. These measurements were performed both postabsorptively and following the ingestion of 50 grams of glucose + 15 grams of protein.

Official Title
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Molecular and Hormonal Responses to Diet-Induced Insulin Resistance

Conditions
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Healthy

Intervention / Treatment
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* Dietary Supplement: High-fat, high-energy diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged between 18 and 40 years Physically active Non-smoker Not taking any medication known to interfere with the study No history of cardiovascular disease or diabetes Weight stable for the last 6 months Exclusion Criteria: Outside of age range Sedentary Smoker Taking medication known to interfere with the study History of cardiovascular disease or diabetes Unstable weight within last 6 months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 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
Intervention Model: Single Group Assignment
Interventional Model Description: 15 healthy individuals were assessed before and after consuming a high-fat, high-energy diet for 7 days.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High-fat diet<br>Participants underwent a 7 day high-fat, high-energy diet intervention with metabolic measurements before and after | Dietary Supplement: High-fat, high-energy diet<br>* Participants consumed a diet that was high in fat and high in energy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in glucose concentration | Venous blood samples were obtained the day before and the day after the 7 day high-fat diet. Glucose was reported as mmol/L. | Immediately before and after the 7 day high-fat diet (i.e., measurements were made 7 days apart) | 
| Change in insulin concentration | Venous blood samples were obtained the day before and the day after the 7 day high-fat diet. Insulin was reported as pmol/L. | Immediately before and after the 7 day high-fat diet (i.e., measurements were made 7 days apart) | 
| Change in glucose kinetics (i.e., rate of appearance and disappearance) assessed using isotope tracers | Glucose kinetics were assessed the day before and the day after the 7 day high-fat diet. Data expressed as umol/kg/min. | Immediately before and after the 7 day high-fat diet (i.e., measurements were made 7 days apart) | 
| Change in skeletal muscle insulin signalling | AKT and AS160 phosphorylation was determined by Western blotting of skeletal muscle. Data are expressed as arbitrary units. | Immediately before and after the 7 day high-fat diet (i.e., measurements were made 7 days apart) | 
| Change in markers of microvascular function | endothelial nitric oxide synthase was determined in terminal arterioles by quantitative immunofluorescence microscopy that was performed on sections of skeletal muscle tissue. Data presented as arbitrary units. | Immediately before and after the 7 day high-fat diet (i.e., measurements were made 7 days apart) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change intramuscular triglyceride content | Intramuscular triglyceride content was determined by quantitative immunofluorescence microscopy that was performed on sections of skeletal muscle tissue. Data presented as arbitrary units. | Immediately before and after the 7 day high-fat diet (i.e., measurements were made 7 days apart) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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High-fat diet, Insulin, Glucose, Muscle, eNOS, Isotopes