Altered immune system in offspring of rat maternal vertical sleeve gastrectomy

Abstract

Obesity in women results in reduced fertility and increased complications during pregnancy. Vertical sleeve gastrectomy (VSG) effectively reduces weight, type 2 diabetes, and dyslipidemia, but is also associated with preterm and small-for-gestational age births. The mechanism by which VSG influences fetal development remains unknown. Here we hypothesize that previously reported immune changes during rat VSG pregnancy are reflected long term in the immune system of the offspring. Offspring of VSG and sham dams were evaluated at postnatal day (PND) 21 and PND60. At PND21, VSG pups have lower numbers of circulating B lymphocytes compared with sham pups ( P < 0.05) and have lower transcription of lymphocyte marker Ptprc ( P < 0.01) in the spleen, while other lymphocyte populations measured are not different. Total plasma IgG is higher ( P < 0.01) and C-reactive protein is lower ( P < 0.05) in VSG offspring compared with sham offspring at PND21. The central nervous system of VSG pups is also affected at PND21, having higher expression of Il1b mRNA ( P < 0.05) and higher immunoreactivity of microglia marker, IBA1, in the hypothalamus. At PND60, the immune-hematological differences are not present; however, mRNA expression of Il1b is elevated ( P < 0.001) in the spleen of VSG offspring along with markers of T cells. These data suggest that the immune system of VSG offspring is compromised early in life, but rebounds after weaning and may even become hyperactive. Future work is needed to determine whether the immune system of VSG offspring is capable of mounting a proper defense and whether other aspects of development are affected.