Abstract Dilated cardiomyopathy (DCM) has been in the literature and news because of the recent opinion-based journal articles and public releases by regulatory agencies. DCM is commonly associated with a genetic predisposition in certain dog breeds and can also occur secondary to other diseases and nutritional deficiencies. Recent communications in veterinary journals have discussed a potential relationship between grain-free and/or novel protein diets to DCM, citing a subjective increase in DCM in dog breeds that are not known to have a genetic predisposition for the disease. This literature review describes clinical presentations of DCM, common sequelae, treatment and preventative measures, histopathologic features, and a discussion of the varied etiological origins of the disease. In addition, current literature limitations are addressed, in order to ascertain multiple variables leading to the development of DCM. Future studies are needed to evaluate one variable at a time and to minimize confounding variables and speculation. Furthermore, to prevent sampling bias with the current FDA reports, the veterinary community should be asked to provide information for all cases of DCM in dogs. This should include cases during the same time period, regardless of the practitioner’s proposed etiology, due to no definitive association between diets with specific characteristics, such as, but not limited to, grain-free diets and those containing legumes, novel protein diets, and those produced by small manufacturers to DCM in dogs. In summary, in order to determine if certain ingredients, categories of diets, or manufacturing processes are related to an increased risk of DCM, further studies investigating these variables are necessary.

Low-birth-weight (LBWT) neonates experience restricted muscle growth in their perinatal life. Our aim was to investigate the mechanisms that contribute to slower skeletal muscle growth of LBWT neonatal pigs. Twenty-four 1-day old male LBWT (816 ± 55 g) and normal-birth-weight (NBWT; 1,642 ± 55 g) littermates (n = 12) were euthanized to collect blood and longissimus dorsi (LD) muscle subsamples. Plasma glucose, insulin, and insulin-like growth factor-I (IGF-I) were lower in LBWT compared with NBWT pigs. Muscle IGF-I mRNA expression were lower in LBWT than NBWT pigs. However, IGF-I receptor mRNA and protein abundance was greater in LD of LBWT pigs. Abundance of myostatin and its receptors, and abundance and phosphorylation of smad3 were lower in LBWT LD by comparison with NBWT LD. Abundance of eukaryotic initiation factor (eIF) 4E binding protein 1 and mitogen-activated protein kinase-interacting kinases was lower in muscle of LBWT pigs compared with NBWT siblings, while eIF4E abundance and phosphorylation did not differ between the two groups. Furthermore, phosphorylation of ribosomal protein S6 kinase 1 (S6K1) was less in LBWT muscle, possibly due to lower eIF3e abundance. In addition, abundance and phosphorylation of eIF4G was reduced in LBWT pigs by comparison with NBWT littermates, suggesting translation initiation complex formation is compromised in muscle of LBWT pigs. In conclusion, diminished S6K1 activation and translation initiation signaling are likely the major contributors to impaired muscle growth in LBWT neonatal pigs. The upregulated IGF-I R expression and downregulated myostatin signaling seem to be compensatory responses for the reduction in protein synthesis signaling.

Low birth weight (LBWT) is consistently associated with impaired postnatal muscle growth in mammals. Satellite cell (SC)‐mediated myonuclear incorporation precedes protein accumulation in the early stages of postnatal muscle development and growth. The objective of this study was to investigate proliferation and differentiation of SCs and the regulation of protein synthesis signaling in response to insulin‐like growth factor (IGF)‐I stimulation in SC‐derived myotubes of LBWT neonatal pigs. SCs isolated from Longissimus dorsi muscle of LBWT and NBWT pigs (3‐d‐old, n = 8) were cultured and induced to proliferate and differentiate to myotubes in vitro. On day 3 of differentiation, myotubes were fasted in serum‐free media for 3 h and treated with human recombinant R3‐insulin‐like growth factor‐I (rh IGF‐I) at 0, 25, and 50 ng × mL−1 for 30 min. There was no difference in proliferation rates of SCs from LBWT and NBWT pigs. However, LBWT SC fusion was 15% lower (P ≤ 0.05) without a difference in MyoD or myogenin mRNA expression in comparison with NBWT pigs, suggesting SCs are not intrinsically different between the two groups. IGF‐Ι stimulation at physiological concentrations activated downstream effectors of mTOR similarly in myotubes from LBWT and NBWT pigs. However, abundance of ribosomal protein S6 kinase 1(S6K1) was lower in myotubes of LBWT compared to their NBWT siblings (P ≤ 0.05). These results indicate that the modest reduction in SC fusion and S6K1 expression are not the major contributors to the impaired postnatal muscle growth of LBWT pigs.

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Low birth weight (LBWT) neonates experience restricted fetal muscle development and impaired postnatal muscle growth. Our previous data suggest that protein synthesis is lower while protein degradation is not different in skeletal muscle of LBWT compared to normal birth weight (NBWT) neonatal pigs. We hypothesized that decreased protein synthesis in skeletal muscle of LBWT pigs is a consequence of dysfunction of insulin‐like growth factor (IGF) signaling cascade. Twenty four LBWT and NBWT male pigs were euthanized to collect blood and longissimus dorsi (LD) muscle samples. Plasma IGF‐I concentration was measured using a commercial ELISA kit, mRNA expression by real‐time PCR and protein expression and phosphorylation by western blot. Plasma IGF‐I concentration and mRNA expression of IGF‐I and IGF binding protein 5 (IGFBP 5) were lower in LD muscle of LBWT pigs (P < 0.05). However, mRNA and protein expression of IGF‐I receptor was higher in the LD muscle of LBWT compared to NBWT pigs (P < 0.05). Protein expression of eukaryotic initiation factor 4E binding protein 1 (4EBP1) and phosphorylation of ribosomal protein S6 kinase 1 (S6K1) were lower in LD muscle of LBWT compared to their NBWT siblings (P < 0.05). These results suggest that in spite of the increased abundance of IGF‐I receptor in muscles of LBWT pigs, there is a reduction in the expression of downstream effectors of IGF‐I. As a result, IGF signaling is compromised and could contribute to impaired postnatal muscle growth in LBWT compared to NBWT neonatal pigs.Support or Funding InformationVirginia Agricultural Experiment Station and the Hatch Program of the National Institute of Food and Agriculture, U.S. Department of Agriculture (S.W. El‐Kadi)