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Huffman 2014 Diabetologia

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Huffman KM, Koves TR, Hubal MJ, Abouassi H, Beri N, Bateman LA, Stevens RD, Ilkayeva OR, Hoffman EP, Muoio DM, Kraus WE (2014) Metabolite signatures of exercise training in human skeletal muscle relate to mitochondrial remodelling and cardiometabolic fitness. Diabetologia 57:2282-95.

Β» PMID: 25091629

Huffman KM, Koves TR, Hubal MJ, Abouassi H, Beri N, Bateman LA, Stevens RD, Ilkayeva OR, Hoffman EP, Muoio DM, Kraus WE (2014) Diabetologia

Abstract: Targeted metabolomic and transcriptomic approaches were used to evaluate the relationship between skeletal muscle metabolite signatures, gene expression profiles and clinical outcomes in response to various exercise training interventions. We hypothesised that changes in mitochondrial metabolic intermediates would predict improvements in clinical risk factors, thereby offering novel insights into potential mechanisms.

Subjects at risk of metabolic disease were randomised to 6 months of inactivity or one of five aerobic and/or resistance training programmes (n=112). Pre/postintervention assessments included cardiorespiratory fitness (VO2peak), serum triacylglycerols (TGs) and insulin sensitivity (SI). In this secondary analysis, muscle biopsy specimens were used for targeted mass spectrometry-based analysis of metabolic intermediates and measurement of mRNA expression of genes involved in metabolism.

Exercise regimens with the largest energy expenditure produced robust increases in muscle concentrations of evenchain acylcarnitines (median 37–488%), which correlated positively with increased expression of genes involved in muscle uptake and oxidation of fatty acids. Along with free carnitine, the aforementioned acylcarnitine metabolites were related to improvements in VO2peak, TGs and SI (R=0.20– 0.31, p<0.05).Muscle concentrations of the tricarboxylic acid cycle intermediates succinate and succinylcarnitine (R=0.39 and 0.24, p<0.05) emerged as the strongest correlates of SI.

The metabolic signatures of exercise-trained skeletal muscle reflected reprogramming of mitochondrial function and intermediary metabolism and correlated with changes in cardiometabolic fitness. Succinate metabolism and the succinate dehydrogenase complex emerged as a potential regulatory node that intersects with whole-body insulin sensitivity. This study identifies new avenues for mechanistic research aimed at understanding the health benefits of physical activity. β€’ Keywords: Acylcarnitines, Branched-chain amino acids, Metabolomics, Physical activity, Skeletal muscle, Succinate

β€’ O2k-Network Lab: US NC Durham Koves TR


Labels: MiParea: Exercise physiology;nutrition;life style, Patients 


Organism: Human  Tissue;cell: Skeletal muscle