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.
Bariatric surgery is the most effective and durable means of treating obesity and its comorbidities. Women make up 80% of those receiving weight loss surgery and they experience improvements in fertility. Unfortunately, bariatric surgery in the context of pregnancy is associated with complications, including growth restriction and small‐for‐gestational age offspring (SGA). SGA offspring have a greater risk for obesity in adulthood, although the mechanism for this SGA‐induced obesity is unknown. In a rat model of vertical sleeve gastrectomy (VSG), we previously identified reductions during pregnancy in ghrelin, a stomach‐derived hormone that increases appetite and induces growth hormone secretion. Here, we hypothesise that VSG offspring will have altered ghrelin signalling compared to offspring of Sham dams as a result of reduced in utero ghrelin. At postnatal day (PND)21, male and female offspring of dams that have previously received VSG have an increase in mRNA expression for the ghrelin receptor in the hypothalamus compared to Sham offspring, and the expression of GOAT is lower in females compared to males. Liver expression of endogenous ghrelin antagonist, LEAP2, is elevated at PND60 in VSG offspring. Expression of other genes in the growth hormone system (growth hormone‐releasing hormone and growth hormone) were not altered. Plasma levels of total ghrelin at PND21 are also not different between VSG and Sham pups. In adult pups, 1‐hour chow intake of male but not female VSG offspring given is less than Sham offspring when given 50 µg kg‐1 of exogenous ghrelin by i.p. injection. These results indicate that maternal VSG surgery has an impact on ghrelin signalling in offspring and that, as adults, male VSG offspring may be functionally less responsive to ghrelin than controls.
Elevation, standing crop, disturbance and soil fertility often emerge from studies of freshwater plant communities as the dominant environmental factors determining both species richness and species composition. Few studies in North America have investigated the relationship between these factors and species abundance (standing crop) and species composition in the context of invasion by Phragmites australis. This study explores the influence of key abiotic and biotic variables on species abundance and composition across three Lake Erie wetlands differing in hydrology and Phragmites abundance in East Harbor, Ohio, USA. Standing crop for 92 species was related to standard sediment analyses, wave exposure, distance to shoreline, elevation, light interference, species density, and Phragmites standing crop in each of 95 1 Â 1 m quadrats by using canonical correspondence analysis (CCA). Elevation (Axis I) and Phragmites standing crop-soil fertility (Axis II) explained 35.7 and 26.2%, respectively, of the variation in the speciesenvironment relationships. Wave exposure was not a primary component of the first four canonical axes. Axis I was instrumental in describing species composition, separating wet meadow species from marsh species. Axis II was inversely related to species density for both wet meadow and marsh species. These findings generally support prevailing models describing the distribution of wetland plants along environmental gradients. Two discrepancies were noted, however: (1) species density was highest in the most sheltered sites and (2) wave exposure was directly associated with Phragmites standing crop-soil fertility gradient. The structural integrity of Phragmites stems, topographic heterogeneity and differential responses to anthropogenic disturbance may contribute to departure from prevailing multivariate models. This information has direct implications for local and regional wetland managers.
Although bariatric surgery is approved for a woman of child-bearing age with an interest in subsequent pregnancy, reports of in utero growth issues during pregnancy have garnered a closer look at the impact of maternal surgical weight loss on the pre- and postpartum periods. Offspring of dams having received vertical sleeve gastrectomy (VSG) are born small-for-gestational age and have increased risk for metabolic syndrome later in life. Here, we aimed to determine whether the postnatal catch-up growth trajectory of bariatric offspring may be affected by milk composition. Milk samples were collected at postnatal day 15/16 from dams having received VSG surgery and fed a high-fat diet (HFD) (H-VSG), Sham surgery and fed chow (C-Sham), or Sham surgery and fed HFD (H-Sham). Milk obtained from H-VSG dams had elevated glucose (P < 0.05) and significantly reduced triglyceride content (P < 0.01). Milk from H-Sham dams had the lowest amount of milk protein (P < 0.05). Fatty acid composition measured by fractionation was largely not affected by surgery but rather maternal diet. No difference was observed in milk leptin levels; however, insulin, adiponectin, and growth hormone levels were significantly increased in milk from H-VSG animals. H-Sham had the lowest level of immunoglobulin (Ig)A, whereas IgG was significantly reduced in H-VSG. Taken together, the quality of milk from H-VSG dams suggests that milk composition could be a factor in reducing the rate of growth during the lactation period.
Bariatric surgery is on the rise for long-term weight loss and produces various positive metabolic health benefits. The mechanisms that produce surgical weight loss are not yet fully understood. Previous studies showed vertical sleeve gastrectomy prior to gestation resulted in reduced peripheral blood lymphocytes measured during pregnancy due to an undetermined etiology. Further, elevated splenic weight has been associated with vertical sleeve gastrectomy surgery. We hypothesized that perhaps altered splenic filtration was trapping circulating lymphocytes and thus reducing peripheral blood lymphocytes in circulation and contributing to increased spleen weight. We posited whether removal of the spleen concomitant with the stomach surgery may result in an improved immune phenotype. We evaluated female long Evans rats having received Sham surgery or vertical sleeve gastrectomy, with or without splenectomy to determine the contribution of the spleen on metabolic and immune factors after vertical sleeve gastrectomy. Vertical sleeve gastrectomy animals lost significant amounts of body mass and fat mass and ate less in comparison to Sham females during the first five post-operative weeks, but there was no specific effect of the loss of spleen on body mass, fat mass, or food intake. During the post-operative week 6, animals were euthanized and blood recovered for cell sorting of immune cells. There was a reduction in CD3+ total T cells, CD3/CD4+ helper T cells, and CD3/CD8+ cytotoxic T cells, main effect of both bariatric surgery ( P < 0.0001) and splenectomy ( P < 0.01). Furthermore, there was a significant increase in CD45RA+ B cells as a result of splenectomy ( P < 0.001), but a significant reduction in B cells as a result of VSG surgery ( P < 0.05). The changes in total T cells but not B cells were strongly correlated with fat mass. Further studies are needed to understand the cause of the immune changes after surgical weight loss. Impact statement Bariatric surgery and in particular vertical sleeve gastrectomy are the fastest growing means for robust amelioration of the comorbidities of obesity. The ramifications of the surgeries on immune health are of important consequence because of the connectivity of immunity with every organ system. The current work reports on the impact of the surgery on the spleen, thymus, and peripheral blood in a rodent model that mimics human surgical outcomes. We demonstrate altered immune health in the VSG rat.
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