Abstract
We investigated the consequences of mild maternal malnutrition in rat dams, in terms of thymocyte responses and the putative role of leptin. The young progeny of dams submitted to protein deprivation (PD) during lactation showed at 30 days of age lower body and thymus weights, significant alterations in CD4/CD8-defined T cell subsets without modifications in total thymocyte number as well as in proliferative response. Despite, the rats from PD group did not present alterations in leptin circulating levels, the expression of leptin receptor ObRb was enhanced in their thymocytes. This change was accompanied by an increase in leptin signaling response of thymocytes from PD rats, with an increase in JAK2 and STAT3 phosphorylation after leptin stimulation. Thymocytes from PD rats also presented a decreased rate of spontaneous apoptosis when compared to controls. Accordingly, higher expression of anti-apoptotic protein Bcl-2, and lower of pro-apoptotic protein Bax, with no change of pro-apoptotic Bad, and higher pro-caspase 3 content were detected in PD thymocytes. Moreover, thymocytes from PD group exhibited a constitutive higher nuclear content of p65 NF-kB associated to a lower IkB content in the cytoplasm. Finally, although there was no change in ob gene expression in PD thymocytes, a higher mRNA expression for the Ob gene was observed in the thymic microenvironment from PD animals. Taken together, the results show that mild maternal protein deprivation during lactation affects thymic homeostasis, enhancing leptin activity, which in turn protects thymocytes from apoptosis in the young progeny, with possible consequences upon the immune response of these animals in adult life.
Highlights
Epidemiological and experimental studies have demonstrated that maternal nutritional imbalance and metabolic disturbances during critical time windows of development may have a persistent effect on the offspring’s health [1]
To investigate the hypothesis that mild maternal protein deprivation affects the maturation of thymocytes from the young adult offsprings, we evaluated the expression of membrane surface markers in these cells, isolated from control and PD groups
We showed that thymus isolated from PD rats presented higher percentages of mature CD4+ and CD8+ single-positive thymocyte subsets, when compared to the control group
Summary
Epidemiological and experimental studies have demonstrated that maternal nutritional imbalance and metabolic disturbances during critical time windows of development may have a persistent effect on the offspring’s health [1]. It has been demonstrated that nutritional deficiency during early life alters crucial physiological circuits, with changes in hormone receptors [2,3], signaling molecules [4,5,6,7,8] and regulatory enzymes [4,8,9]. We have reported that adult offsprings from dams submitted to protein deprivation during early lactation exhibit an imbalance in insulin and glucocorticoid secretion, which affects the proper development of acute inflammatory responses. This was ascertained by lower leukocyte migration into inflammatory sites, decreased edema formation, and lower expression of the adhesion molecule ICAM1 [10,11]. Besides interfering with insulinmediated responses, maternal protein restriction during lactation interferes with leptin secretion in offsprings, which present higher serum leptin contents and increased leptin receptor expression in the pituitary gland [12,13]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
