Defining the contribution of skeletal muscle pyruvate dehydrogenase α1 to exercise performance and insulin action
| Autor: | Shahriar Tahvilian, Kristoffer Svensson, Julien Ochala, Abha Sathe, Jessica R. Dent, Mulchand S. Patel, Simon Schenk, Vitor F. Martins |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Physiology Endocrinology Diabetes and Metabolism medicine.medical_treatment Mitochondrion Carbohydrate metabolism Athletic Performance Diet High-Fat 03 medical and health sciences Mice 0302 clinical medicine Oxygen Consumption Physiology (medical) Internal medicine Physical Conditioning Animal Exercise performance medicine Animals Insulin Pyruvate Dehydrogenase (Lipoamide) Lactic Acid Muscle Skeletal Mice Knockout Chemistry Skeletal muscle High fat diet Carbohydrate Glucose Tolerance Test Pyruvate dehydrogenase complex Adaptation Physiological Mitochondria Muscle 030104 developmental biology Endocrinology medicine.anatomical_structure Glucose Body Composition Female Insulin Resistance Energy Metabolism 030217 neurology & neurosurgery Muscle Contraction Research Article |
| Zdroj: | American journal of physiology. Endocrinology and metabolism. 315(5) |
| ISSN: | 1522-1555 |
| Popis: | The pyruvate dehydrogenase complex (PDC) converts pyruvate to acetyl-CoA and is an important control point for carbohydrate (CHO) oxidation. However, the importance of the PDC and CHO oxidation to muscle metabolism and exercise performance, particularly during prolonged or high-intensity exercise, has not been fully defined especially in mature skeletal muscle. To this end, we determined whether skeletal muscle-specific loss of pyruvate dehydrogenase alpha 1 ( Pdha1), which is a critical subunit of the PDC, impacts resting energy metabolism, exercise performance, or metabolic adaptation to high-fat diet (HFD) feeding. For this, we generated a tamoxifen (TMX)-inducible Pdha1 knockout (PDHmKO) mouse, in which PDC activity is temporally and specifically ablated in adult skeletal muscle. We assessed energy expenditure, ex vivo muscle contractile performance, and endurance exercise capacity in PDHmKO mice and wild-type (WT) littermates. Additionally, we studied glucose homeostasis and insulin sensitivity in muscle after 12 wk of HFD feeding. TMX administration largely ablated PDHα in skeletal muscle of adult PDHmKO mice but did not impact energy expenditure, muscle contractile function, or low-intensity exercise performance. Additionally, there were no differences in muscle insulin sensitivity or body composition in PDHmKO mice fed a control or HFD, as compared with WT mice. However, exercise capacity during high-intensity exercise was severely impaired in PDHmKO mice, in parallel with a large increase in plasma lactate concentration. In conclusion, although skeletal muscle PDC is not a major contributor to resting energy expenditure or long-duration, low-intensity exercise performance, it is necessary for optimal performance during high-intensity exercise. |
| Databáze: | OpenAIRE |
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