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J Clin Endocrinol Metab. 2018 May 1;103(5):1910-1920. doi: 10.1210/jc.2017-02267.

Metabolic Inflexibility Is an Early Marker of Bed-Rest-Induced Glucose Intolerance Even When Fat Mass Is Stable.

Author information

1
Université de Strasbourg, CNRS, IPHC UMR 7178, Strasbourg, France.
2
3U Diabetes Consortium, Dublin City University, Dublin, Ireland.
3
National Institute for Cellular Biotechnology & School of Health and Human Performance, Dublin City University, Dublin, Ireland.
4
Carmen INSERM U1060, University of Lyon, INRA U1235, Lyon, France.
5
Human Nutrition Research Centre of Rhône-Alpes, Hospices Civils de Lyon, Lyon, France.
6
Université de Montpellier, INRA, UMR 866 Dynamique Musculaire et Métabolisme, Montpellier, France.
7
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, United Kingdom.
8
Institute of Nutritional and Food Sciences, Human Nutrition, University of Bonn, Bonn, Germany.
9
German Aerospace Center (DLR), Institute of Aerospace Medicine, Cologne, Germany.
10
University of Duisburg-Essen, Department of Child and Adolescent Psychiatry, Essen, Germany.
11
Centre National d'Etudes Spatiales, Paris, France.
12
Anschutz Health and Wellness Center, Anschutz Medical Campus, Aurora, Colorado.
13
Division of Endocrinology, Metabolism and Diabetes, University of Colorado, Anschutz Medical Campus, Aurora, Colorado.

Abstract

Context:

The effects of energy-balanced bed rest on metabolic flexibility have not been thoroughly examined.

Objective:

We investigated the effects of 21 days of bed rest, with and without whey protein supplementation, on metabolic flexibility while maintaining energy balance. We hypothesized that protein supplementation mitigates metabolic inflexibility by preventing muscle atrophy.

Design and Setting:

Randomized crossover longitudinal study conducted at the German Aerospace Center, Cologne, Germany.

Participants and Interventions:

Ten healthy men were randomly assigned to dietary countermeasure or isocaloric control diet during a 21-day bed rest.

Outcome Measures:

Before and at the end of the bed rest, metabolic flexibility was assessed during a meal test. Secondary outcomes were glucose tolerance by oral glucose tolerance test, body composition by dual energy X-ray absorptiometry, ectopic fat storage by magnetic resonance imaging, and inflammation and oxidative stress markers.

Results:

Bed rest decreased the ability to switch from fat to carbohydrate oxidation when transitioning from fasted to fed states (i.e., metabolic inflexibility), antioxidant capacity, fat-free mass (FFM), and muscle insulin sensitivity along with greater fat deposition in muscle (P < 0.05 for all). Changes in fasting insulin and inflammation were not observed. However, glucose tolerance was reduced during acute overfeeding. Protein supplementation did not prevent FFM loss and metabolic alterations.

Conclusions:

Physical inactivity triggers metabolic inflexibility, even when energy balance is maintained. Although reduced insulin sensitivity and increased fat deposition were observed at the muscle level, systemic glucose intolerance was detected only in response to a moderately high-fat meal. This finding supports the role of physical inactivity in metabolic inflexibility and suggests that metabolic inflexibility precedes systemic glucose intolerance.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01655979.

PMID:
29546280
DOI:
10.1210/jc.2017-02267
[Indexed for MEDLINE]

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