Ketogenic diet with medium‐chain triglycerides restores skeletal muscle function and pathology in a rat model of Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is an intractable genetic disease associated with progressive skeletal muscle weakness and degeneration. Recently, it was reported that intraperitoneal injections of ketone bodies partially ameliorated muscular dystrophy by increasing satellite cell (SC) proliferati...

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Bibliographic Details
Published in:The FASEB journal 2021-09, Vol.35 (9), p.e21861-n/a
Main Authors: Fujikura, Yuri, Sugihara, Hidetoshi, Hatakeyama, Masaki, Oishi, Katsutaka, Yamanouchi, Keitaro
Format: Article
Language:English
Subjects:
Duchenne muscular dystrophy
ketogenic diet
ketone bodies
nutrition therapy
skeletal muscle
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Summary:Duchenne muscular dystrophy (DMD) is an intractable genetic disease associated with progressive skeletal muscle weakness and degeneration. Recently, it was reported that intraperitoneal injections of ketone bodies partially ameliorated muscular dystrophy by increasing satellite cell (SC) proliferation. Here, we evaluated whether a ketogenic diet (KD) with medium‐chain triglycerides (MCT‐KD) could alter genetically mutated DMD in model rats. We found that the MCT‐KD significantly increased muscle strength and fiber diameter in these rats. The MCT‐KD significantly suppressed the key features of DMD, namely, muscle necrosis, inflammation, and subsequent fibrosis. Immunocytochemical analysis revealed that the MCT‐KD promoted the proliferation of muscle SCs, suggesting enhanced muscle regeneration. The muscle strength of DMD model rats fed with MCT‐KD was significantly improved even at the age of 9 months. Our findings suggested that the MCT‐KD ameliorates muscular dystrophy by inhibiting myonecrosis and promoting the proliferation of muscle SCs. As far as we can ascertain, this is the first study to apply a functional diet as therapy for DMD in experimental animals. Further studies are needed to elucidate the underlying mechanisms of the MCT‐KD‐induced improvement of DMD.
ISSN:0892-6638
1530-6860
DOI:10.1096/fj.202100629R