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Obesity, a complex condition that involves genetic, environmental, and behavioral factors, is a non-infectious pandemic that affects over 650 million adults worldwide with a rapidly growing prevalence. A major contributor is the consumption of high-fat diets, an increasingly common feature of modern diets. Maternal obesity results in an increased risk of offspring developing obesity and related health problems; however, the impact of maternal diet on the adipose tissue composition of offspring has not been evaluated. Here, we designed a generational diet-induced obesity study in female C57BL/6 mice that included maternal cohorts and their female offspring fed either a control diet (10% fat) or a high-fat diet (45% fat) and examined the visceral adipose proteome. Solubilizing proteins from adipose tissue is challenging due to the need for high concentrations of detergents; however, the use of a detergent-compatible sample preparation strategy based on suspension trapping (S-Trap) enabled label-free quantitative bottom-up analysis of the adipose proteome. We identified differentially expressed proteins related to lipid metabolism, inflammatory disease, immune response, and cancer, providing valuable molecular-level insight into how maternal obesity impacts the health of offspring. Data are available via ProteomeXchange with the identifier PXD042092. [ABSTRACT FROM AUTHOR]

Aim: Gasdermin-D (GSDMD) and pannexin-1 (PANX1), which are proinflammatory proteins, may be involved in the pathogenesis of complications in pregnant women with obesity. We aimed to investigate the expression of GSDMD and PANX1 biochemically in samples of maternal omental and placental tissue obtained from pregnant women with or without obesity, and their correlation with maternal, obstetric, and fetal/neonatal variables. Methods: The prospective observational study included 79 pregnant women who underwent elective cesarean sections with a pregnancy between 37 and 41 weeks from December 2021 to April 2022. They were divided into three study groups according to their body mass index (BMI): normal weight (with a BMI 30) (n=26). Omental and placental GSDMD and PANX1 levels were measured by enzyme-linked immunosorbent assay between the groups. Results: In the homogenate of omental tissue, the median levels of GSDMD and PANX1 protein in the overweight and obese groups were significantly lower than those in the normal weight groups (p=0.0154 and p=0.0184, respectively). In the placental tissue samples, the median levels of GSDMD and PANX1 proteins in the normal weight, overweight, and obese groups were similar. Conclusion: GSDMD and PANX1 expressions were shown for the first time in the omentum and placenta together; which has the potential to be used as a predictive and diagnostic test panel after further studies in obese pregnant women.

Aim: Gasdermin-D (GSDMD) and pannexin-1 (PANX1), which are proinflammatory proteins, may be involved in the pathogenesis of complications in pregnant women with obesity. We aimed to investigate the expression of GSDMD and PANX1 biochemically in samples of maternal omental and placental tissue obtained from pregnant women with or without obesity, and their correlation with maternal, obstetric, and fetal/neonatal variables. Methods: The prospective observational study included 79 pregnant women who underwent elective cesarean sections with a pregnancy between 37 and 41 weeks from December 2021 to April 2022. They were divided into three study groups according to their body mass index (BMI): normal weight (with a BMI <25) (n=25), overweight (BMI between 25 and 30) (n=28), and obese (with a BMI >30) (n=26). Omental and placental GSDMD and PANX1 levels were measured by enzyme-linked immunosorbent assay between the groups. Results: In the homogenate of omental tissue, the median levels of GSDMD and PANX1 protein in the overweight and obese groups were significantly lower than those in the normal weight groups (p=0.0154 and p=0.0184, respectively). In the placental tissue samples, the median levels of GSDMD and PANX1 proteins in the normal weight, overweight, and obese groups were similar. Conclusion: GSDMD and PANX1 expressions were shown for the first time in the omentum and placenta together; which has the potential to be used as a predictive and diagnostic test panel after further studies in obese pregnant women. [ABSTRACT FROM AUTHOR]

The peritoneal cavity, especially the omentum, is a common site for gastric cancer metastasis, representing advanced disease stage and poor prognosis. Here, we studied the effects of omental tissue on gastric cancer tumor progression in vitro and in vivo. Utilizing in vitro models, we found that omental tissue secreted factors increased gastric cancer cellular growth (by 30–67%, P < 0.05), motility (>8-fold, P < 0.05), invasiveness (>7-fold, P < 0.05) and chemoresistance to platinum-based chemotherapeutic agents (>1.2-fold for oxaliplatin and >1.6-fold for cisplatin, P < 0.05). Using a robust proteomic approach, we identified numerous molecules secreted into the omental tissue conditioned medium (CM) which may promote gastric cancer cellular aggressiveness (i.e., IL-6, IL-8, MMP9, FN1, and CXCL-5). Next, an in vivo xenograft mouse model showed an increased human gastric adenocarcinoma tumor volume of cells co-cultured with human omental tissue secreted factors; 1.6 ± 0.55 vs. 0.3 ± 0.19 cm3 (P < 0.001), as well as increased angiogenesis. Finally, exosomes were isolated from human omental tissue CM of gastric cancer patients. These exosomes were taken up by gastric cancer cells enhancing their growth (>8-fold, P < 0.01) and invasiveness (>8-fold, P < 0.001). Proteomic analysis of the content of these exosomes identified several established cancer- related proteins (i.e., IL-6, IL-8, ICAM-1, CCl2, and OSM). Taken together, our findings imply that the omentum play an active role in gastric cancer metastasis. The data also describe specific cytokines that are involved in this cross talk, and that omental tissue- derived exosomes may contribute to these unique cellular interactions with gastric cancer cells. Further studies aimed at understanding the biology of gastric cancer intra peritoneal spread are warranted. Hopefully, such data will enable to develop future novel therapeutic strategies for the treatment of metastatic gastric cancer.

The peritoneal cavity, especially the omentum, is a common site for gastric cancer metastasis, representing advanced disease stage and poor prognosis. Here, we studied the effects of omental tissue on gastric cancer tumor progression in vitro and in vivo. Utilizing in vitro models, we found that omental tissue secreted factors increased gastric cancer cellular growth (by 30–67%, P < 0.05), motility (>8-fold, P < 0.05), invasiveness (>7-fold, P < 0.05) and chemoresistance to platinum-based chemotherapeutic agents (>1.2-fold for oxaliplatin and >1.6-fold for cisplatin, P < 0.05). Using a robust proteomic approach, we identified numerous molecules secreted into the omental tissue conditioned medium (CM) which may promote gastric cancer cellular aggressiveness (i.e., IL-6, IL-8, MMP9, FN1, and CXCL-5). Next, an in vivo xenograft mouse model showed an increased human gastric adenocarcinoma tumor volume of cells co-cultured with human omental tissue secreted factors; 1.6 ± 0.55 vs. 0.3 ± 0.19 cm3 (P < 0.001), as well as increased angiogenesis. Finally, exosomes were isolated from human omental tissue CM of gastric cancer patients. These exosomes were taken up by gastric cancer cells enhancing their growth (>8-fold, P < 0.01) and invasiveness (>8-fold, P < 0.001). Proteomic analysis of the content of these exosomes identified several established cancer- related proteins (i.e., IL-6, IL-8, ICAM-1, CCl2, and OSM). Taken together, our findings imply that the omentum play an active role in gastric cancer metastasis. The data also describe specific cytokines that are involved in this cross talk, and that omental tissue- derived exosomes may contribute to these unique cellular interactions with gastric cancer cells. Further studies aimed at understanding the biology of gastric cancer intra peritoneal spread are warranted. Hopefully, such data will enable to develop future novel therapeutic strategies for the treatment of metastatic gastric cancer. [ABSTRACT FROM AUTHOR]