SFEBES2025 Poster Presentations Metabolism, Obesity and Diabetes (68 abstracts)
Voluntary exercise normalises the preferential metabolic energy source in a mouse model of down syndrome
Cristina Perez-Ternero 1 , Fenn Cullen 1 , Pinku Halder 2 , Martin Irmler 3 , Nini Nguyen 1 , Ruoyan Xu 1 , Mara Dierssen 4 , Yann Herault 5 , Johannes Beckers 3 , Marie-Claude Potier 2 , GO-DS21 consortium 1 & Li F Chan 1
1Queen Mary University of London, London, United Kingdom; 2Paris Brain Institute, Paris, France; 3Helmholtz Zentrum München, Neuherberg, Germany; 4Centre for Genomic Regulation, Barcelona, Spain; 5Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France
Introduction: Down syndrome (DS) is associated with chronotropic incompetence and gait disturbances which reduces exercise capacity in this population. Moreover, mitochondrial dysfunction has been described in several cell types in DS, and has been linked to metabolic inflexibility and poorer exercise endurance in the general population. However, the effect of aging on exercise capacity in DS and on metabolic substrate utilisation remains to be fully explored.
Methods: Male and female Dp1Tyb (DS) and wild-type (WT) mice were used in this study at 9 weeks, 18 weeks and 14 months of age for calorimetric studies (TSE Phenomaster). Exercise to exhaustion was evaluated on a treadmill at 28 weeks of age. Gastrocnemius tissue was used to evaluate the oxygen consumption rate (OCR) in an Oxygraph-2k system, and for metabolomics and transcriptomics studies.
Results: Despite similar ambulatory activity, male and female DS mice had a steeper decline in voluntary exercise on the running wheel with age compared to WT. Worse endurance was confirmed by treadmill exercise to exhaustion showing reduced VO2, and VO2Max, and higher plasma lactate. Calorimetric studies revealed a preference for carbohydrates as a metabolic substrate in young (9 and 18 weeks) male DS animals and both sexes of aged DS animals, which was normalised by voluntary exercise on the running wheel. OCR revealed mitochondrial dysfunction in the gastrocnemius muscle, confirmed by transcriptomic analyses.
Conclusions: DS was associated with a faster physical capacity decline, potentially linked to mitochondrial dysfunction of the gastrocnemius muscle leading to metabolic inflexibility. Regular voluntary exercise normalised the preferential metabolic source of energy. This data can help tailor exercise routine recommendations in the DS population aiming at improving or preventing metabolic diseases such as obesity and diabetes.
Volume 109
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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