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Open AccessArticle

β-Hydroxybutyrate Increases Exercise Capacity Associated with Changes in Mitochondrial Function in Skeletal Muscle

Laboratorio de Investigación en Nutrición y Actividad Física (LABINAF), Instituto de Nutrición y Tecnología de los Alimentos (INTA), Universidad de Chile, Santiago 8380492, Chile
Advanced Center for Chronic Diseases (ACCDiS), Facultad de Ciencias Químicas y Farmacéuticas & Facultad de Medicina, Universidad de Chile, Santiago 8380492, Chile
Escuela de Kinesiologia, Facultad de Medicina, Universidad Finis Terrae, Santiago 7500000, Chile
Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago 8330025, Chile
Corporación Centro de Estudios Científicos de las Enfermedades Crónicas (CECEC), Santiago 7860201, Chile
Department of Internal Medicine (Cardiology Division), University of Texas Southwestern Medical Center, Dallas, TX 75390-8573, USA
Authors to whom correspondence should be addressed.
Nutrients 2020, 12(7), 1930;
Received: 28 May 2020 / Revised: 23 June 2020 / Accepted: 24 June 2020 / Published: 29 June 2020
(This article belongs to the Special Issue Metabolic Adaptations to Diet and Physical Activity)
β-hydroxybutyrate is the main ketone body generated by the liver under starvation. Under these conditions, it can sustain ATP levels by its oxidation in mitochondria. As mitochondria can modify its shape and function under different nutritional challenges, we study the chronic effects of β-hydroxybutyrate supplementation on mitochondrial morphology and function, and its relation to exercise capacity. Male C57BL/6 mice were supplemented with β-hydroxybutyrate mineral salt (3.2%) or control (CT, NaCl/KCl) for six weeks and submitted to a weekly exercise performance test. We found an increase in distance, maximal speed, and time to exhaustion at two weeks of supplementation. Fatty acid metabolism and OXPHOS subunit proteins declined at two weeks in soleus but not in tibialis anterior muscles. Oxygen consumption rate on permeabilized fibers indicated a decrease in the presence of pyruvate in the short-term treatment. Both the tibialis anterior and soleus showed decreased levels of Mitofusin 2, while electron microscopy assessment revealed a significant reduction in mitochondrial cristae shape in the tibialis anterior, while a reduction in the mitochondrial number was observed only in soleus. These results suggest that short, but not long-term, β-hydroxybutyrate supplementation increases exercise capacity, associated with modifications in mitochondrial morphology and function in mouse skeletal muscle. View Full-Text
Keywords: ketone bodies; β-hydroxybutyrate; mitochondrial morphology; skeletal muscle; endurance ketone bodies; β-hydroxybutyrate; mitochondrial morphology; skeletal muscle; endurance
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Monsalves-Alvarez, M.; Morales, P.E.; Castro-Sepulveda, M.; Sepulveda, C.; Rodriguez, J.M.; Chiong, M.; Eisner, V.; Lavandero, S.; Troncoso, R. β-Hydroxybutyrate Increases Exercise Capacity Associated with Changes in Mitochondrial Function in Skeletal Muscle. Nutrients 2020, 12, 1930.

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