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Complex I is bypassed during high intensity exercise.

ABSTRACT: Human muscles are tailored towards ATP synthesis. When exercising at high work rates muscles convert glucose to lactate, which is less nutrient efficient than respiration. There is hence a trade-off between endurance and power. Metabolic models have been developed to study how limited catalytic capacity of enzymes affects ATP synthesis. Here we integrate an enzyme-constrained metabolic model with proteomics data from muscle fibers. We find that ATP synthesis is constrained by several enzymes. A metabolic bypass of mitochondrial complex I is found to increase the ATP synthesis rate per gram of protein compared to full respiration. To test if this metabolic mode occurs in vivo, we conduct a high resolved incremental exercise tests for five subjects. Their gas exchange at different work rates is accurately reproduced by a whole-body metabolic model incorporating complex I bypass. The study therefore shows how proteome allocation influences metabolism during high intensity exercise.

SUBMITTER: Nilsson A

PROVIDER: S-EPMC6838197 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Complex I is bypassed during high intensity exercise.

Nilsson Avlant A Björnson Elias E Flockhart Mikael M Larsen Filip J FJ Nielsen Jens J

Nature communications 20191107 1

Human muscles are tailored towards ATP synthesis. When exercising at high work rates muscles convert glucose to lactate, which is less nutrient efficient than respiration. There is hence a trade-off between endurance and power. Metabolic models have been developed to study how limited catalytic capacity of enzymes affects ATP synthesis. Here we integrate an enzyme-constrained metabolic model with proteomics data from muscle fibers. We find that ATP synthesis is constrained by several enzymes. A ...[more]

PMID: 31699973

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Project description:PURPOSE:Whether the benefits of exercise during chemotherapy continue into survivorship is not well-known. Here, the aim was to examine the effects of two exercise interventions on self-reported health-related and objectively measured physiological outcomes 12 months following commencement of chemotherapy. METHODS:Two hundred and forty women with breast cancer stage I-IIIa were randomized to 16 weeks of high-intensity aerobic interval training combined with either resistance training (RT-HIIT), or moderate-intensity aerobic training (AT-HIIT), or to usual care (UC). PRIMARY OUTCOME:cancer-related fatigue (CRF); secondary outcomes: quality of life (QoL), symptom burden, muscle strength, cardiorespiratory-fitness, body mass, and return to work. RESULTS:Compared to UC, both RT-HIIT and AT-HIIT significantly counteracted increases in total CRF (ES = - 0.34; ES = - 0.10), daily life CRF (ES=-0.76; ES=-0.50, and affective CRF (ES=-0.60; ES=-0.39). Both RT-HIIT and AT-HIIT reported significantly lower total symptoms (ES = - 0.46, ES = - 0.46), and displayed gains in lower limb (ES = 0.73; ES = 1.03) and handgrip muscle strength (surgery side ES = 0.70, ES = 0.71; non-surgery side ES = 0.57, ES = 0.59). AT-HIIT displayed significant reductions in body mass (ES = - 0.24), improved QoL: role (ES = 0.33) and emotional functioning (ES = 0.40), and a larger proportion had returned to work (p = 0.02) vs UC. CONCLUSION:These findings emphasize the beneficial effects of supervised high-intensity exercise during chemotherapy to improve the health and to reduce societal costs associated with prolonged sick leave for patients with breast cancer several months following chemotherapy. IMPLICATIONS FOR CANCER SURVIVORS:These findings provide important information with substantial positive consequences for breast cancer survivorship. High-intensity exercise programs during chemotherapy and support to maintain physical activity can be a powerful strategy to manage or prevent many of the short- and long-term adverse effects of treatment for the increasing cohort of cancer survivors.

Project description:High-intensity interval exercise (HIIE) has been reported to be more beneficial for physical adaptation than low-to-moderate exercise intensity. Recently, it is becoming increasingly evident that circulating miRNAs (c-miRNAs) may distinguish between specific stress signals imposed by variations in the duration, modality, and type of exercise. The aim of this study is to investigate whether or not HIIE is superior to vigorous-intensity continuous exercise (VICE), which is contributing to develop effective fitness assessment. Twenty-six young males were enrolled, and plasma samples were collected prior to exercise and immediately after HIIE or distance-matched VICE. The miRNA level profiles in HIIE were initially determined using TaqMan Low Density Array (TLDA). And the differentially miRNAs levels were validated by stem-loop quantitative reverse-transcription PCR (RT-qPCR). Furthermore, these selective c-miRNAs were measured for VICE. Our results showed that some muscle-related miRNAs levels in the plasma, such as miR-1, miR-133a, miR-133b, and miR-206 significantly increased following HIIE or VICE compared to those at rest (P < 0.05), and there was only a significant reduction in miR-1 level for HIIE compared to VICE (P < 0.05), while no significant differences were observed for other muscle-related miRNAs between both exercises (P > 0.05). In addition, some tissue-related or unknown original miRNA levels, such as miR-485-5p, miR-509-5p, miR-517a, miR-518f, miR-520f, miR-522, miR-553, and miR-888, also significantly increased (P < 0.05) in both exercises compared to rest. However, no significant differences were found between both exercises (P > 0.05). Overall, endurance exercise assessed in this study both led to significant increases in selective c-miRNAs of comparable magnitude, suggesting that both types of endurance exercise have general stress processes. Accordingly, the similar responses to both acute exercises likely indicate both exercises can be used interchangeably. Further work is needed to reveal the functional significance and signaling mechanisms behind changes in c-miRNA turnover during exercise.

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Complex I is bypassed during high intensity exercise.

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Complex I is bypassed during high intensity exercise.

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