Abstract
Several human epidemiological and animal studies suggest that a maternal low-protein (MLP) diet affects skeletal muscle (SM) health in the offspring. However, effect of combined prenatal to postnatal protein restriction (chronic PR) and prenatal to perinatal protein restriction (PR) with postnatal rehabilitation maternal protein restriction (MPR) on protein quality control (PQC) processes and proteolysis in the offspring remains poorly understood. The current study explored the impact of chronic PR and MPR on SM protein degradation rates, chaperones, unfolded protein response (UPR), ubiquitin-proteasome system (UPS), autophagy, and apoptosis, in the adult offspring. Wistar rats were randomly assigned to a normal protein (NP; 20% casein), or low-protein (LP; 8% casein) isocaloric diets from 7 weeks prior to breeding through weaning. Offspring born to NP dams received the same diet (NP offspring) while a group of LP offspring remained on LP diet and another group was rehabilitated with NP diet (LPR offspring) from weaning for 16 weeks. LP offspring displayed lower body weight, lean mass, and myofiber cross-sectional area than NP. Furthermore, LP offspring demonstrated increased total protein degradation, urinary 3-methyl histidine, ER stress, autophagy, UPS components, proteasomal activity, muscle atrophy markers, and apoptosis-related proteins than NP. However, MPR showed little or no effect on muscle proteolysis, UPR, UPS, autophagy, apoptosis, and muscle atrophy in LPR offspring. These results indicate that exposure to chronic PR diets induces muscle atrophy and accelerates SM proteolysis via augmenting PQC processes in the offspring, while MPR shows little or no effect.