Ketogenic diet slows down mitochondrial myopathy progression in mice

Area of Science:

• Biochemistry
• Mitochondrial Biology
• Neurology

Background:

• Mitochondrial dysfunction causes severe neurodegenerative and neuromuscular diseases.
• Current treatments for these progressive disorders are ineffective.
• Ketogenic diet (KD) shows potential in cell cultures for mitigating mitochondrial DNA (mtDNA) mutations.

Purpose of the Study:

• To investigate the therapeutic potential of the ketogenic diet (KD) in a mouse model of progressive late-onset mitochondrial myopathy.
• To assess the effects of KD on disease progression, muscle pathology, and metabolic changes.

Main Methods:

• Utilized the transgenic Deletor mouse model, which mimics age-related mtDNA deletions and respiratory chain (RC) deficiency.
• Administered long-term pre-symptomatic and shorter-term post-symptomatic KD.
• Evaluated disease progression using morphological, metabolomic, and lipidomic analyses.

Main Results:

• KD significantly decreased the number of cytochrome c oxidase-negative muscle fibers and prevented mitochondrial ultrastructural abnormalities.
• The diet normalized most metabolic and lipidomic alterations to wild-type levels.
• KD induced mitochondrial biogenesis and restored liver lipid profiles, without significantly altering mtDNA quantity or quality.

Conclusions:

• Mitochondrial myopathy is associated with widespread metabolic disturbances.
• The ketogenic diet demonstrates efficacy in slowing disease progression and improving metabolic parameters in a mouse model.
• These findings suggest KD as a promising therapeutic strategy for late-onset mitochondrial myopathies.