Day-Night Rhythm in Human Skeletal Muscle

Day-night Rhythm in Human Skeletal Muscle Metabolism

This study evaluates the existence of a day-night rhythm in skeletal muscle energy metabolism in healthy lean subjects. Subjects will stay at the research facility for 44 hours with a standardized living protocol during which several measurements of skeletal muscle and whole body energy metabolism will be performed.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2; Insulin Resistance
• Intervention / Treatment: Other: Standardized living protocol

Detailed Description

Recent evidence from both observational and experimental studies indicates that disobeying our normal day-night rhythm negatively influences our metabolic and cardiovascular health, possibly leading to obesity and type 2 diabetes mellitus (T2DM). An important hallmark of obesity and T2DM is a decreased skeletal muscle mitochondrial function. Interestingly, recent research indicates that also skeletal muscle mitochondrial function under the influence of a day-night rhythm. The main objective of this study is to investigate the presence of a day-night rhythm in skeletal muscle energy metabolism (in particular mitochondrial function) of healthy young participants. Therefore, subjects will stay at the research unit for 44 hours, with standardized meals and sleeping time. During this period we will take five muscle biopsies, perform indirect calorimetry measurements and blood draws.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Maastricht, Netherlands
    • Maastricht University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Caucasian
• Healthy (as determined by dependent physician based on medical questionnaire)
• Male
• Age: 18-35 years
• Normal BMI (18-25 kg/m2)
• Regular sleeping time (normally 7-9h daily)

Exclusion Criteria:

• Extreme early bird or extreme night person (score ≤30 or ≥70 on MEQ-SA questionnaire)
• Heavily varying sleep-wake rhythm
• Shiftwork during last 3 months
• Travel across >1 time zone in the last 3 months
• Engagement in exercise > 2 hours total per week
• Using >400mg caffeine daily
• Smoking
• Unstable body weight (weight gain or loss > 3kg in the last 3 months)
• Significant food allergies/intolerance (seriously hampering study meals)
• Participation in another biomedical study within 1 month before the first study visit
• Any contra-indication to Magnetic Resonance Imaging (MRI) scanning

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
Other: Standardized living protocol; Subjects are kept at the research facility to adhere to a standardized living protocol, mimicking a normal daily living situation. During the study, multiple tests will be performed, including muscle biopsies, blood draws, MRS measurements and indirect calorimetry.	Other: Standardized living protocol; Subjects stay at the research facility for 44 hours and adhere to a standard sleeping, eating and activity protocol. During this protocol, multiple measurements will be performed including skeletal muscle biopsies (m. vastus lateralis), blood draws, indirect calorimetry and MRS measurements.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Day-night rhythm in skeletal muscle mitochondrial respiration	O2-flux (pmol/mg/s) measured with high resolution respirometry upon administration of different substrates	40 hours.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Day-night rhythm in whole-body energy metabolism	Energy expenditure (kJ/min), glucose oxidation (g/min) and fat oxidation (g/min) measured by indirect calorimetry	40 hours.
Day-night rhythm in muscle DNA, mRNA and protein levels of markers involved in molecular clock and mitochondrial metabolism.	Quantify mRNA and protein levels by qPCR or micro-array and Western blots	40 hours.
Day-night rhythm of in markers of normal day-night rhythm (cortisol, melatonin, core body temperature)	Blood cortisol and melatonin levels and core body temperature measured by an ingested telemetric pill.	measured during the 2nd study day
Day-night rhythm in blood metabolic compounds (e.g. glucose, insulin, FFA's, cholesterol)		measured during the 2nd study day
Day-night rhythm of molecular clock mRNA and protein levels in blood PBMC's	Measured by qPCR and Western Blots	measured during the 2nd study day
Change in liver volume and liver lipid concentration during the day	Measured by Magnetic Resonance Imaging and -Spectroscopy (MRI/MRS). Lipid signals in the MRS spectra will be quantified while suppressing the strong water signal in the region of interest (right liver lobe)	First study day 6 PM, second study day 7 AM

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Investigators: Principal Investigator: Patrick Schrauwen, PhD, Professor

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: September 24, 2014
• First Submitted That Met QC Criteria: October 6, 2014
• First Posted (Estimate): October 10, 2014

Study Record Updates

• Last Update Posted (Estimate): September 7, 2015
• Last Update Submitted That Met QC Criteria: September 4, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Keywords: Circadian Rhythm
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Hyperinsulinism; Diabetes Mellitus, Type 2; Insulin Resistance
• Other Study ID Numbers: METC143027; NL49363.068.14 (Registry Identifier: Toetsing Online)