Altered immune system in offspring of rat maternal vertical sleeve gastrectomy

Abstract

Women undergoing metabolic surgery for weight loss see many improvements in health, including reduced adiposity and treatment of type 2 diabetes. Fertility is also improved by bariatric surgery and the number of large for gestational day births are reduced. Unfortunately, fetal demise and low birth weights are more prevalent following bariatric surgery, and children born small for gestational age are at an increased risk of obesity as adults. We have replicated these findings in a rat model of vertical sleeve gastrectomy (VSG), however, the origin of these poor outcomes in offspring remains unknown. We have previously reported a reduction in plasma T lymphocytes in pregnant female VSG rats compared to pregnant Sham surgery rats, and increased circulating Immunoglobulin G (IgG) protein. We also reported in the placenta increased mRNA levels of interleukin 1 β (IL1B), interleukin 1 receptor antagonist, and matrix metalloproteinase 9 in VSG animals compared to Shams as well as increased TUNEL positive cells indicating apoptosis. We have currently expanded our work in the placenta, finding that mRNA for B cell marker, PTPRC, and cytotoxic T cell marker, CD8A, is elevated in VSG dams. In postnatal day 21 (PND21) pups, we measure lower circulating B lymphocytes in both males and females born to VSG dams compared to pups born to Sham dams, as well as elevated total IgG, while T cells and monocytes were not altered. In the pup hypothalamus at PND21, IL1B mRNA is elevated and this persists until PND120 in males fed chow diet. Transcription of other pro‐inflammatory cytokines such as interleukin 6 and tumor necrosis factor alpha, is not altered in the hypothalamus. These data suggest that VSG surgery alters the immune system in utero and these changes may affect immune health postnatally. Future work will determine what signalling pathways transduce this immune response and if they contribute to low birth weight and metabolic syndrome in offspring. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Ghrelin signalling is dysregulated in male but not female offspring in a rat model of maternal vertical sleeve gastrectomy

“…In the VSG model, chow‐fed pups have reduced body weight up to PND30 but, during the subsequent month, the body weights of the VSG and controls appear to normalise. This pattern of reduced body weight has been shown in other reports using this model 36,37 …”

“…After surgeries, rats were maintained on standard chow diet (Figure 1). Body weight and composition data for these animals have been reported previously 37 …”

“…Body weight and composition data for these animals have been reported previously. 37 Male rats (300-350 g) were maintained under similar housing condition on standard rat chow (Teklad 8640; Envigo) and used as studs.…”

“…This pattern of reduced body weight has been shown in other reports using this model. 36,37 In the weigh-suckle-weigh paradigm performed in the PND14…”

Curbing Obesity from One Generation to Another: the Effects of Bariatric Surgery on the In Utero Environment and Beyond

“…We next asked if the immune system of the postnatal offspring was affected by maternal immune changes. At PND21, B lymphocytes in the peripheral blood were reduced while total IgG was elevated in offspring of VSG dams compared to the offspring of Sham dams [134]. At the same time point, markers of inflammation in the brain were elevated, including Il1b and microglial marker, IBA1 [134].…”