An obesogenic diet alters muscle function in mdx mice

Duchenne muscular dystrophy (DMD) is a progressive muscle degenerative disease that occurs in 1 in 5000 boys born worldwide. DMD is caused by the absence of a functional dystrophin protein, a major structural protein within muscle. Boys with DMD commonly develop obesity and insulin resistance (IR) compounded by limited mobility and extended treatment with glucocorticoids; however, the extent to which obesity and/or IR affect dystrophic pathology are unknown. We hypothesized that a high fat/high sucrose diet (HF/HSD) would further antagonize disease-related losses in muscle function and that these losses would be partially offset by prednisolone (Pred). To test this hypothesis, male C57 and mdx mice were fed a control diet (CD) or HF/HSD for 19 weeks, with or without Pred supplementation, followed by in vitro muscle function tests. Insulin resistance was confirmed via glucose and insulin tolerance tests. The absolute and relative weight of gastrocnemius, soleus, extensor digitorum longus (EDL), and tibialis anterior muscles were increased in mdx groups compared to C57 (p<0.01) but decreased in mdx groups treated with Pred compared to untreated mdx groups (p<0.01). Muscle mass was similar between dietary treatment groups in C57 and mdx mice. Specific tension in the diaphragm was decreased by disease (p<0.01) but was not altered by diet or Pred treatment. Diaphragms from mdx mice were less fatigue resistant than from C57 mice (p<0.01). Within mdx diaphragms, the addition of Pred and/or HF/HSD decreased fatigue resistance compared to mice maintained on CD. The C57 CD/Pred group was less fatigable than other C57 groups (p<0.01). In the soleus, tetanic force was increased in mdx compared to C57 mice (p<0.01) but was decreased by the HF/HSD in mdx groups (p=0.05). Soleus specific tension was similar between C57 and mdx groups but was decreased in mdx HF/HSD groups compared to CD (p<0.01). In the soleus, mdx groups were less resistant to fatigue than C57 groups (p<0.01); however, the HF/HSD and/or Pred treatment did not further promote fatigue in C57 or mdx mice. In EDL, tetanic force was increased in mdx groups compared to C57 groups (p<0.01), and in both C57 and mdx mice, Pred-treated groups had decreased force compared to untreated groups (p<0.01), but force was not impacted by diet. Specific tension was decreased in mdx groups compared to C57 (p<0.01). Within mdx groups, specific tension of Pred-treated groups was increased compared to untreated groups (p<0.01). The EDL was more resistant to contraction-induced injury in C57 compared to mdx mice. Within mdx mice, the HF/HSD and Pred-treated groups were more resistant to eccentric injury than mdx CD/no Pred mice (p<0.01). These data suggest that a HF/HSD and/or Pred can alter parameters of muscle function. This work is supported by Muscular Dystrophy Association grant #962344. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.