Nutrition, Exercise and Muscle Metabolism in Obesity
Influence of Pre- or Post-exercise Food Intake on Muscle Metabolism in Obesity
Study Overview
Detailed Description
Two thirds of the adult US population is overweight or obese and the prevention and treatment of obesity is a key priority due to the strain on societal health, well-being and economic prosperity. Obesity is associated with insulin resistance characterized by a reduced ability of insulin to stimulate glucose uptake into skeletal muscle and by hyperglycaemia. Obesity and insulin resistance are major risk factors for cardiovascular disease and type 2 diabetes. Weight loss through caloric restriction and increasing physical activity levels are the mainstay of non-surgical/pharmacological treatment for obesity. Weight loss can reduce insulin resistance although sustainable weight loss is difficult to achieve. Physical activity can help with weight maintenance but perhaps surprisingly, carefully controlled longitudinal studies in obese patients indicate aerobic exercise training in the absence of weight loss has no or at best modest impact on peripheral insulin resistance.
One mechanism by which regular aerobic exercise training ensures high peripheral insulin sensitivity in endurance trained individuals is via stimulation of intramyocellular triglyceride turnover and muscle fat oxidation, which maintains low muscle levels of fatty acid metabolites known to interfere with insulin-stimulated muscle glucose uptake (e.g., fatty acyl CoA, diacyglycerols, ceramides). Indirect evidence suggests intramyocellular triglyceride can be utilized as fuel during aerobic exercise in obese individuals, at least in the overnight-fasted state. However, the influence of overnight-fasted vs. fed-state exercise on intramyocellular triglyceride utilization and muscle oxidative adaptation has not been studied in obesity. This is important to study as fed-state exercise, as compared to overnight-fasted exercise, blunts exercise-associated increases in intramyocellular triglyceride utilization, oxidative gene expression, long-term adaptation of muscle oxidative capacity and resistance to high fat diet induced impairments in oral glucose tolerance in lean individuals.
Thus, the presence or timing of recent nutrition with respect to exercise could be a critical factor explaining the inability of aerobic exercise training per se to improve peripheral insulin sensitivity in longitudinal studies in obese populations. Exercising in the overnight-fasted state could optimize metabolic adaptation to training in obese individuals with long-term benefits for reduced insulin resistance and cardio-metabolic disease risk.
Study Type
Enrollment (Anticipated)
Phase
- Not Applicable
Contacts and Locations
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Anthropometry/Body Size:
i. Overweight (White European populations, BMI 25-29.9 kg/m2 or Asian populations, BMI 23-27.4 kg/m2) and have a high waist circumference (European, Sub-Saharan Africans and Eastern Mediterranean and middle east [Arab] men ≥ 94 cm [37 inches], women ≥ 80 cm [31.5 inches]; South Asian, Chinese, Japanese, and ethnic south and central Americans men ≥ 90 cm [35 inches], women ≥ 80 cm [31.5 inches]) or ii. Class I obesity (White European populations, BMI 30-34.9 kg/m2 or Asian populations, BMI 27.5-35 kg/m2).
- Weight stable i.e. (±2 kg) for >3 months before enrolment
- Sedentary i.e. no regular engagement in physical activity
- Diagnosis and general health: Good general health defined as no known cardiovascular or metabolic disease
- Compliance: understands and is willing, able and likely to comply with all study procedures and restrictions
- Consent: demonstrates understanding of the study and willingness to participate as evidenced by voluntary written informed consent.
Exclusion Criteria:
- Answering "YES" to any question on the Screening Form
- Hypertension (≥140/90 mmHg)
- Any ECG Abnormalities
- Current participation in another clinical study
- Current or recent smoker (last 30 days)
- Past history of substance abuse, engagement in uncommon eating practices (e.g., sustained periods of fasting) and taking prescription or non-prescription medication (e.g., beta-blockers, insulin or thyroxine) or supplements that may influence normal metabolic responses.
- Participants who have previously (within 5 years of the present study) had 4 or more muscle biopsies obtained from the thigh quadriceps region will be ineligible
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Pre-exercise food
Pre-exercise food provision
|
Participants will complete two morning exercise sessions.
One will be performed in the overnight fasted-state (i.e.
no food or drink, except water, from 10pm the evening before) and the other will be performed in the fed-state having received a breakfast by the research team before exercise.
|
|
Experimental: Post-exercise food
Post-exercise food provision
|
Participants will complete two morning exercise sessions.
One will be performed in the overnight fasted-state (i.e.
no food or drink, except water, from 10pm the evening before) and the other will be performed in the fed-state having received a breakfast by the research team before exercise.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Intramuscular triglyceride use during exercise (arbitrary units)
Time Frame: Up to 12 months
|
Does exercising in the overnight-fasted state promote greater breakdown of intramuscular fat than performing exercise in the fed state?
|
Up to 12 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Gene expression
Time Frame: Up to 12 months
|
The influence of pre- versus post-exercise feeding on the expression of genes related to exercise.
training adaptation.
Accordingly, muscle samples will be analysed using qPCr for expression of genes (relative mRNA) involved in fat metabolism (FAT/CD36, CPT1, βHAD), mitochondrial biogenesis (PGC-1α) and substrate oxidation (COXIV, CYT C, CS, SDH).
|
Up to 12 months
|
Collaborators and Investigators
Sponsor
Collaborators
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- RG_15-036
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