Molecular and Hormonal Responses to Diet-Induced Insulin Resistance

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Dietary supplement: High-fat, high-energy diet

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

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: High-fat diet; Participants underwent a 7 day high-fat, high-energy diet intervention with metabolic measurements before and after	Dietary supplement: High-fat, high-energy diet; Participants consumed a diet that was high in fat and high in energy

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Loughborough University

Publications and helpful links

General Publications

• Parry SA, Turner MC, Woods RM, James LJ, Ferguson RA, Cocks M, Whytock KL, Strauss JA, Shepherd SO, Wagenmakers AJM, van Hall G, Hulston CJ. High-Fat Overfeeding Impairs Peripheral Glucose Metabolism and Muscle Microvascular eNOS Ser1177 Phosphorylation. J Clin Endocrinol Metab. 2020 Jan 1;105(1):dgz018. doi: 10.1210/clinem/dgz018.

Study record dates

Study Major Dates

• Study Start (Actual): March 2, 2015
• Primary Completion (Actual): May 22, 2018
• Study Completion (Actual): May 22, 2018

Study Registration Dates

• First Submitted: March 12, 2019
• First Submitted That Met QC Criteria: March 15, 2019
• First Posted (Actual): March 18, 2019

Study Record Updates

• Last Update Posted (Actual): March 18, 2019
• Last Update Submitted That Met QC Criteria: March 15, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Insulin; Glucose; Muscle; High-fat diet; eNOS; Isotopes
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperinsulinism; Insulin Resistance
• Other Study ID Numbers: R13-P171

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