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

Area of Science:

• Exercise Physiology
• Mitochondrial Biology
• Nutritional Biochemistry

Background:

• β-hydroxybutyrate is a key ketone body produced during starvation, supporting ATP production via mitochondrial oxidation.
• Mitochondria dynamically adapt their morphology and function in response to nutritional cues.
• Understanding these adaptations is crucial for optimizing metabolic health and performance.

Purpose of the Study:

• To investigate the chronic effects of β-hydroxybutyrate supplementation on mitochondrial morphology and function.
• To determine the relationship between β-hydroxybutyrate supplementation and exercise capacity.
• To elucidate the impact on skeletal muscle adaptations.

Main Methods:

• Male C57BL/6 mice received β-hydroxybutyrate mineral salt or control supplementation for six weeks.
• Weekly exercise performance tests were conducted to assess endurance.
• Mitochondrial morphology (electron microscopy) and function (oxygen consumption) were analyzed in skeletal muscle.

Main Results:

• Exercise capacity (distance, speed, time to exhaustion) increased after two weeks of β-hydroxybutyrate supplementation.
• Fatty acid metabolism and OXPHOS proteins decreased in soleus muscle; mitochondrial morphology showed reduced cristae and number.
• Mitofusin 2 levels decreased in both tibialis anterior and soleus muscles.

Conclusions:

• Short-term β-hydroxybutyrate supplementation can transiently enhance exercise capacity in mice.
• These improvements are linked to specific alterations in mitochondrial morphology and function within skeletal muscles.
• Long-term supplementation does not sustain these exercise performance benefits.