A medium-chain triglyceride-containing ketogenic diet (MCTKD) exacerbates cardiomyopathy in a CRISPR/Cas9 gene-edited rat model for Duchenne muscular dystrophy (DMD), according to a new study published in Scientific Reports. The results come as a follow-up from a group that had previously reported that MCTKD improved skeletal muscle function in the same rat model.

Compared to rats fed a normal diet, the MCTKD-fed rats showed a number of statistically worse cardiovascular measurements including a prolonged QRS duration (17.7 ms vs 13.3 ms), a lower R-wave amplitude, decreased left ventricular fractional shortening, and an increase in the ratio of heart weight to body weight. Progression of cardiac fibrosis was also observed in the MCTKD-fed rats.

Echocardiography revealed decreased left ventricular systolic and diastolic function in the MCTKD rats compared to the normal diet rats. Differences were also observed in several strain rate variables including radial strain rate S-peak, longitudinal strain rate E-peak, and transverse strain rate E-peak.


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Cardiomyocyte necrosis, infiltration of mononuclear cells, and fibrosis were also discovered on cardiac histopathological analysis. 

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“The present findings demonstrated that MCTKD dietary intervention in DMD rats, which dramatically improved the skeletal muscle myopathy, did not improve their cardiomyopathy,” the authors said.

“Further studies are needed to explore the underlying mechanisms for these differences and to explore modified dietary treatment options that improve skeletal and cardiac muscles simultaneously.”

The authors supplied 3 possible explanations for why there was a difference between the results in skeletal and cardiac muscle tissue. The first was that the 2 muscle tissues utilize different metabolic energy sources with skeletal muscle in DMD generally transitioning to slow-type fibers that utilize fat components for energy while cardiac cells generally switch to glucose oxidation once affected by DMD-related cardiomyopathy. In these circumstances, the low carbohydrate, high-fat ketogenic diet might cause energy deficiency in cardiac cells.

Another factor mentioned was that as skeletal muscle function improves, this may increase the amount of exercise performed by the rats which could accelerate cardiomyopathy damage. The final factor mentioned was that injured skeletal muscle generally regenerates rather quickly while the regenerative abilities of adult mammalian cells are rather limited.

Reference

Fujikura Y, Kimura K, Yamanouchi K, et al. A medium-chain triglyceride containing ketogenic diet exacerbates cardiomyopathy in a CRISPR/Cas9 gene-edited rat model with Duchenne muscular dystrophy. Sci Rep. 2022;12(1):11580. doi:10.1038/s41598-022-15934-9