TLR4 knockout can improve dysfunction of β-cell by rebalancing proteomics disorders in pancreas of obese rats

Yan, Sunjie; Jiang, Zhen; Cheng, Ling; Lin, Youfen; Fan, Beibei; Luo, Liufen; Yan, Yuanli; Yang, Liyong; Shen, Xiaodong

doi:10.1007/s12020-019-02106-5

Cited by 15 publications

(10 citation statements)

References 33 publications

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“…However, scientific evidence confirming this model is still lacking. Although we are not aware of any studies which directly demonstrated elevated LPS levels in the pancreas during obesity-associated PDAC development, other studies have suggested the importance of LPS for β-cell function in obese rats with deficiency in TLR4, the receptor for LPS [97]. In another report, administration of LPS to mice which express oncogenic Kras specifically in pancreatic acinar cells caused severe chronic pancreatitis and neoplastic PanIN lesions [98], further highlighting the importance of LPS for PDAC development, although the contribution of macrophages in LPS-treated mice was not addressed.…”

Section: Pancreatic Stromal Macrophages In the Obese Statementioning

confidence: 93%

Pancreatic Macrophages: Critical Players in Obesity-Promoted Pancreatic Cancer

Teper

Eibl

2020

Cancers

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Obesity is a known risk factor for the development of pancreatic cancer, one of the deadliest types of malignancies. In recent years it has become clear that the pancreatic microenvironment is critically involved and a contributing factor in accelerating pancreatic neoplasia. In this context obesity-associated chronic inflammation plays an important role. Among several immune cells, macrophages have been shown to contribute to obesity-induced tissue inflammation. This review article summarizes the current knowledge about the role of pancreatic macrophages in early pancreatic cancer development. It describes the heterogenous origin and mixture of pancreatic macrophages, their role in pancreatic endocrine and exocrine pathology, and the impact of obesity on islet and stromal macrophages. A model is postulated, by which during obesity monocytes are recruited into the pancreas, where they are polarized into pro-inflammatory macrophages that drive early pancreatic neoplasia. This occurs in the presence of local inflammatory, metabolic, and endocrine signals. A stronger appreciation and more detailed knowledge about the role of macrophages in early pancreatic cancer development will lead to innovative preventive or interceptive strategies.

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Section: Pancreatic Stromal Macrophages In the Obese Statementioning

confidence: 93%

Pancreatic Macrophages: Critical Players in Obesity-Promoted Pancreatic Cancer

Teper

Eibl

2020

Cancers

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“…Microbial alterations in PDAC featured an increase of certain pathogens and LPS-producing bacteria [230]. Although, to our knowledge, no studies have been published that directly measured LPS levels in the pancreas of obese subjects with PDAC, other reports using obese rats with deficiency in TLR4 have implicated an important role of LPS for the pancreatic β-cell function in [231]. Furthermore, exogenous administration of LPS to mice with oncogenic Kras expression in pancreatic acinar cells led to chronic pancreatitis and neoplastic PanIN formation [58].…”

Section: Gut Microbiomementioning

confidence: 99%

Obesity and Pancreatic Cancer: Insight into Mechanisms

Eibl

2021

Cancers

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The prevalence of obesity in adults and children has dramatically increased over the past decades. Obesity has been declared a chronic progressive disease and is a risk factor for a number of metabolic, inflammatory, and neoplastic diseases. There is clear epidemiologic and preclinical evidence that obesity is a risk factor for pancreatic cancer. Among various potential mechanisms linking obesity with pancreatic cancer, the adipose tissue and obesity-associated adipose tissue inflammation play a central role. The current review discusses selected topics and mechanisms that attracted recent interest and that may underlie the promoting effects of obesity in pancreatic cancer. These topics include the impact of obesity on KRAS activity, the role of visceral adipose tissue, intrapancreatic fat, adipose tissue inflammation, and adipokines on pancreatic cancer development. Current research on lipocalin-2, fibroblast growth factor 21, and Wnt5a is discussed. Furthermore, the significance of obesity-associated insulin resistance with hyperinsulinemia and obesity-induced gut dysbiosis with metabolic endotoxemia is reviewed. Given the central role that is occupied by the adipose tissue in obesity-promoted pancreatic cancer development, preventive and interceptive strategies should be aimed at attenuating obesity-associated adipose tissue inflammation and/or at targeting specific molecules that mechanistically link adipose tissue with pancreatic cancer in obese patients.

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“…For RPPA protein expression, we identified 6 BMI-related proteins (YWHAE, FN1, PRDX1, PRKCA, BAK1, and ANXA7) only in ESCA (Supplementary Table S 2 ). Previously study report Mapk14-Ywhae signaling disorders in obese rats pancreas and increased YWHAE signaling promotes esophageal squamous carcinoma cell invasion [ 38 , 39 ]. Dysregulated FN1 was identified in obese adipose tissue while high FN1 expression was associated with esophageal cancer [ 40 , 41 ].…”

Section: Resultsmentioning

confidence: 99%

Body mass index-associated molecular characteristics involved in tumor immune and metabolic pathways

Chen

Yao

et al. 2020

Cancer Metab

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Background Overweight or obesity has been evidenced as an important risk factor involved in the incidence, mortality, and therapy response of multiple malignancies. However, the differences between healthy and obesity tumor patients at the molecular and multi-omics levels remain unclear. Methods Our study performed a comprehensive and multidimensional analysis in fourteen tumor types of The Cancer Genome Atlas (TCGA) and found body mass index (BMI)-related genes in multiple tumor types. Furthermore, we compared composite expression between normal, overweight, and obese patients of each immune cell subpopulation and metabolism gene subset. Statistical significance was calculated via the Kruskal-Wallis rank-sum test. Results Our analysis revealed that BMI-related genes are enriched in multiple tumor-related biological pathways involved in intracellular signaling, immune response, and metabolism. We also found the different relationships between BMI and different immune cell infiltration and metabolic pathway activity. Importantly, we found that many clinically actionable genes were BMI-affect genes. Conclusion Overall, our data indicated that BMI-associated molecular characteristics involved in tumor immune and metabolic pathways, which may highlight the clinical importance of considering BMI-associated molecular signatures in cancer precision medicine.

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TLR4 knockout can improve dysfunction of β-cell by rebalancing proteomics disorders in pancreas of obese rats

Cited by 15 publications

References 33 publications

Pancreatic Macrophages: Critical Players in Obesity-Promoted Pancreatic Cancer

Pancreatic Macrophages: Critical Players in Obesity-Promoted Pancreatic Cancer

Obesity and Pancreatic Cancer: Insight into Mechanisms

Body mass index-associated molecular characteristics involved in tumor immune and metabolic pathways

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