Brief Communication: Sexual dimorphic expression of myostatin and follistatin like-3 in a rat trans-generational under-nutrition model

Abstract

The detrimental effects of maternal under-nutrition during gestation on fetal development are well known with an increased propensity of metabolic disorders identified in the adult offspring. Understanding exactly how and by which molecular pathways inadequate nutrition can impact upon offspring phenotype is critical and necessary for the development of treatment methods and ultimately prevention of any negative health effects. Myostatin, a negative regulator of muscle development, has recently been shown to effect glucose homeostasis and fat deposition. The involvement of myostatin in glucose metabolism and adipogenesis thus supports its ability to act in the continued alterations to the postnatal phenotype of the offspring. This hypothesis was examined in the current study using a trans-generational gestationally under-nourished rat model exposed to a high-fat (HF) diet post-weaning. The body weight, body fat, plasma glucose and insulin concentrations of the offspring, both male and female, were investigated in relation to the protein expression of myostatin and its main inhibitor; follistatin like-3 (FSTL-3), in skeletal muscle of mature offspring. Sexual dimorphism was clearly evident in the majority of these measures, including myostatin and FSTL-3 expression. Generally males displayed higher (P < 0.05) myostatin precursor and dimer expression than females, which was especially apparent (P < 0.01) in both chow and HF trans-generationally undernourished (UNAD) groups. In females only, myostatin precursor and dimer expression was altered by both trans-generational under-nutrition and postnatal diet. Overall FSTL-3 expression did not differ between sexes, although difference between sexes within certain treatments and diets were evident. Most notably, HF fed UNAD females had higher (P < 0.05) FSTL-3 expression than HF fed UNAD males. The former group also displayed higher (P < 0.01) FSTL-3 expression compared to all other female groups. In summary, myostatin may prove to be a key mediator of the effects of inadequate prenatal nutrition, independently or in combination with a high-fat postnatal diet on offspring phenotype. Consequently, further study of myostatin may provide a novel therapeutic pathway for the treatment of metabolic disorders; however, it is vital that the influence of nutrition and gender should be taken into consideration.

Method Development for the Detection of Human Myostatin by High-Resolution and Targeted Mass Spectrometry

“…Identifying the different forms of myostatin will allow for a better understanding of the potential availability (precursor) or activity (pro-peptide) of myostatin. In support of the need to discriminate between the different forms of the myostatin protein is our previous work (by Western blot) that identified marked differences in the expression of the myostatin precursor and dimer forms due to diet or gender . Furthermore, the ability for the myostatin pro-peptide to bind and inhibit the function of the myostatin dimer (active form) adds to the need to identify the forms of the myostatin protein. ,, Understanding the expressions of the different forms of myostatin will provide a better idea of the role that this protein has in contributing to disease pathways as well as in targeting antagonistic and agonistic treatments for myostatin action.…”

“…The current gold standard proteomic methods for detecting myostatin are Western blot (protein extractions) or ELISA (for serum studies). Our previous work using Western blot analyses identified variations in the expression of myostatin precursor and dimer levels with changes in diet and gender . We propose the use of a targeted approach to discriminate between the different myostatin protein forms through the analysis of individual peptides by tandem mass spectrometry.…”

Maternal protein restriction during pregnancy induces CCAAT/enhancer-binding protein (C/EBPβ) expression through the regulation of histone modification at its promoter region in female offspring rat skeletal muscle

“…35 Maternal under-nutrition has been reported to manipulate the expression of myostatin, a negative regulator of muscle development that has recently been shown to effect fat deposition. 36 High concentration of intramuscular fat content is highly related with Type 2 diabetes. 37 In our study, the induced C/EBPβ expression that occurred in female puberty rats subjected to maternal low protein diet may provide novel information about the effect of maternal nutrition on fat deposition during postnatal muscle development, implying an increased risk of insulin insensitivity 15 and diabetes.…”

Maternal low-protein diet affects myostatin signaling and protein synthesis in skeletal muscle of offspring piglets at weaning stage

“…Muscle MSTN can be programmed by neonatal underfeeding [13] or can serve as a key mediator of inadequate prenatal nutrition [14] in rats. Feeding LP diet to sows throughout gestation and lactation produced offspring pigs with altered skeletal muscle MSTN expression distinctively at weaning and finishing stages [15].…”