Insulin sensitivity and metabolic flexibility decrease in response to bed rest, but the temporal and causal adaptations in human skeletal muscle metabolism are not fully defined. Here, we use an integrative approach to assess human skeletal muscle metabolism during bed rest and provide a multi-system analysis of how skeletal muscle and the circulatory system adapt to short- and long-term bed rest (German Clinical Trials: DRKS00015677). We uncover that intracellular glycogen accumulation after short-term bed rest accompanies a rapid reduction in systemic insulin sensitivity and less GLUT4 localization at the muscle cell membrane, preventing further intracellular glycogen deposition after long-term bed rest. We provide evidence of a temporal link between the accumulation of intracellular triglycerides, lipotoxic ceramides, and sphingomyelins and an altered skeletal muscle mitochondrial structure and function after long-term bed rest. An intracellular nutrient overload therefore represents a crucial determinant for rapid skeletal muscle insulin insensitivity and mitochondrial alterations after prolonged bed rest.
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Immunofluorescence microscopy in this study shows that GLUT-4 protein expression is fibre-type specific within a muscle. It is postulated that both fibre-type-dependent and fibre-type-independent factors affect GLUT-4 expression.
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Muscle fiber-type specific expression of UCP3-protein is reported here for the firts time, using immunofluorescence microscopy
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High consumption of carbohydrates is linked to metabolic syndrome, possibly via the endogenous formation of advanced glycated end-products. Many Dutch elementary school children have a carbohydrate intake of >130g/day, the estimated minimum requirement. In this observational study, 126 Dutch elementary school children (5-12y of age) from two schools differing in frequency of gym lessons (2 or 5 times a week) were included. In all participants, height, weight, waist circumference, autofluorescence of skin glycated end-products (AGE-score), sports activity and carbohydrate consumption were recorded once. Sports activities in leisure time differentiated participants in ‘sportsmen’ and ‘non-sportsmen’. Carbohydrate intake and AGE score were positively associated in non-sportsmen (p<0.003), but negatively in sportsmen (p<0.002). In sportsmen, but not in non-sportsmen (p>0.50), a positive association was found (p<0.002) between carbohydrate intake and subject age. The intake of total carbohydrate and carbohydrates from juices and soft drinks was lower (p<0.001) at the Wassenberg School relative to the Alexander School. Based on waist to height ratio, >95% of the children had normal fat mass. No correlations were found between waist to height ratio or BMI and carbohydrate intake. Waist to height ratio was positively associated with BMI (p<0.001)) and subject age (p<0.001). Of all principal parameters, AGE score is most affected by being sportsmen or not (p<0.001). This study indicates that an increased intake of carbohydrates can be counteracted by sufficient physical activity (>2.5 hours per week). This implies that skin autofluorescence is a fast and non-invasive method to screen children for life style.
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