The intrauterine environment plays a crucial role during fetal development and affects the health of the adult in later stages [1]. Accumulating evidence demonstrates that the composition of diet during critical periods of development could influence the offspring's body weight (BW), morphology, and biochemistry of the tissues [2], [3], [4], [5]. Reports from human studies and animal models have shown that a maternal low-protein (MLP) diet is associated with lower BW and the development of metabolic diseases, including diabetes [6], hypertension [3], hyperlipidemia, and obesity [7] in the offspring. In the same line, combined prenatal to postnatal protein restriction (PR) or chronic PR leads to changes in structure and function of organs in the offspring, such as kidney [8] and liver [9,10].

The skeletal muscle (SM) accounts for approximately 40% of body mass and is one of the most vulnerable organ to undernutrition during critical stages of pregnancy [4,11,12]. Undernourishment during gestation and lactation affects the SM development [13]. MLP diet has been shown to influence muscle fiber development and density in young offspring [14]. Furthermore, MLP diets reduced the muscle fiber number and neuromuscular junctions and affected the mechanical properties of SM and fiber type composition in the offspring [15]. Additionally, it has been shown that MLP diets alter the expression of metabolic and regulatory genes [16], fiber-type composition, and enzymatic capacities in the SM of the progeny [17].

Maintaining functional protein homeostasis (proteostasis) or protein quality control (PQC) is a lifelong challenge for cellular health. However, proteostasis is constantly jeopardized by several factors originating from pathological, metabolic, and environmental threats. Molecular chaperones, unfolded protein response (UPR), autophagy, and ubiquitin-proteasome system (UPS) constitute the PQC machinery [18]. The collapse of PQC promotes proteotoxic stress and deteriorates cellular functionality and organismal viability. The balance between muscle protein synthesis and degradation pathways can determine SM mass and performance. The imbalance in proteostasis pathways leads to muscle mass loss and muscle weakness, called muscle atrophy. It has been well established that the UPS degrades the myofibrillar proteins and contributes to muscle atrophy [19]. Recently, it has been shown that maternal programming is related to the activation of UPR in the pancreas [20]. Further, MLP diets induced alterations in UPR components in the liver of the rat offspring [21]. Also, MLP diets activated autophagy and amino acid response pathway in the SM of mothers during gestation [22]. Furthermore, MLP diets have been shown to decrease protein synthesis and affect myostatin signalling in offspring SM at weaning [23]. MLP during pregnancy and lactation followed by a normal protein (NP) diet-induced changes in SM morphology but did not affect the expression of crucial myogenic factors in the offspring [24]. Another study reported that MPR during lactation has no effect on the expression of crucial myogenic factors in the offspring [25]. Further, effect of PR in non-pregnant rats for a shorter period on proteolysis was reported [26]. Additionally, several experimental studies solely focused on PR during gestation and/or lactation and do not mimic human condition in much of undeveloped, developing countries where malnutrition is not only confined to fetal life but rather a lifelong condition. Thus, understanding the impact of chronic PR along with maternal protein restriction (MPR) on SM is warranted.

However, the effect of chronic PR (combined prenatal to postnatal PR) and PR during premating, pregnancy, and lactation, followed by the NP diets by the offspring, after weaning (MPR) on SM proteolysis in the offspring has not been investigated. Additionally, key processes involved in PQC and proteolysis such as molecular chaperones, UPR, UPS, and myogenesis in MLP diets-induced muscle atrophy in the offspring remains poorly understood. In this background, we explored the effect of chronic PR and MPR on SM proteolysis and PQC machinery in adult offspring.