Severe consequences of a high-lipid diet include hydrogen sulfide dysfunction and enhanced aggression in glioblastoma

Silver, Daniel J.; Roversi, Gustavo; Bithi, Nazmin; Wang, Sabrina; Troike, Katie; Neumann, Chase; Ahuja, Grace; Reizes, Ofer; Brown, J. Mark; Hine, Christopher; Lathia, Justin D.

doi:10.1172/jci138276

Cited by 41 publications

(40 citation statements)

References 65 publications

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“…In contrast to the above data, in a recent report by Silver and colleagues, data curated and downloaded from The Cancer Genome Atlas (TCGA), CBS mRNA levels did not find differences in mRNA expression between normal breast tissue (n = 291) versus breast cancer tissue (n = 1085) [ 55 ]. This comparison – similarly to the case in colon and ovarian cancer analysis from the same TCGA dataset where it failed to reveal differences – did not compare tumor tissue with matching surrounding tissue, but, rather, compared two different sets of tissues, in this case, with very different patient group size.…”

Section: Cbs Expression In Various Human Cancers: Correlation With Cl...mentioning

confidence: 94%

“…However, in a recent report by Silver and colleagues, using data curated from the GEPIA dataset, CBS mRNA levels were compared in normal colon (n = 349) versus colon adenocarcinoma (n = 275). In this comparison (which, however, did not compare tumor tissue with matching surrounding tissue, but, rather, compared two different sets of tissues), no significant difference in CBS mRNA levels was reported [ 55 ].…”

Section: Cbs Expression In Various Human Cancers: Correlation With Cl...mentioning

confidence: 99%

“…1200 vs. 2000 days in the high and low CBS expressor groups, respectively ( Fig. 2 F) [ 55 ]. A more recent report also reported a similar difference, with patients expressing CBS mRNA at a lower level associated with better clinical outcomes ( Fig.…”

Section: Cbs Expression In Various Human Cancers: Correlation With Cl...mentioning

confidence: 99%

“…3 C); the difference was statistically significant (p < 0.05) in an analysis conducted by Silver and colleagues from another cancer mRNA database comparing 92 low-CBS mRNA expressor and 93 high-CBS mRNA expressor ovarian serous cyst adenocarcinoma patients ( Fig. 3 D) [ 55 ]. The data in the Human Protein Atlas also tended to be associated with better 5-year survival of low-CBS mRNA expressor ovarian cancer patients, compared to high CBS-expressors ( Fig.…”

Section: Cbs Expression In Various Human Cancers: Correlation With Cl...mentioning

confidence: 99%

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Emerging roles of cystathionine β-synthase in various forms of cancer

Ascenção¹,

Szabó²

2022

Redox Biology

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Section: Cbs Expression In Various Human Cancers: Correlation With Cl...mentioning

confidence: 94%

Section: Cbs Expression In Various Human Cancers: Correlation With Cl...mentioning

confidence: 99%

Section: Cbs Expression In Various Human Cancers: Correlation With Cl...mentioning

confidence: 99%

Section: Cbs Expression In Various Human Cancers: Correlation With Cl...mentioning

confidence: 99%

See 2 more Smart Citations

Emerging roles of cystathionine β-synthase in various forms of cancer

Ascenção¹,

Szabó²

2022

Redox Biology

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“…Intracranial implantation experiments with syngeneic tumor cell lines were performed as previously described 42 . 6-week-old C57Bl/6J mice were anesthetized using inhaled isoflurane and an insulin syringe attached to a stereotaxic apparatus was used to inject cells into the left hemisphere at a depth of approximately 3.5mm.…”

Section: Intracranial Tumor Implantationmentioning

confidence: 99%

Tumor cell-intrinsic HFE drives glioblastoma growth

Troike

Silver

Ghosh

et al. 2022

Preprint

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Background: Glioblastoma (GBM) tumor cells modulate expression of iron-associated genes to enhance iron uptake from the surrounding microenvironment, driving proliferation and tumor growth. The homeostatic iron regulator (HFE) gene, encoding the iron sensing HFE protein, is upregulated in GBM and correlates with poor survival outcomes. However, the molecular mechanisms underlying these observations remain unclear. Identification of pathways for targeting iron dependence in GBM tumors is therefore a critical area of investigation. Methods: We interrogated the impact of cell-intrinsic Hfe expression on proliferation and tumor growth through genetic loss and gain of function approaches in syngeneic mouse glioma models. We determined the expression of iron-associated genes and their relationship with survival in GBM using public datasets and identified differentially expressed pathways in Hfe knockdown cells through Nanostring transcriptional profiling. Results: Loss of Hfe induced apoptotic cell death in vitro and inhibited tumor growth in vivo while overexpression of Hfe accelerated both proliferation and tumor growth. Analysis of iron gene signatures in Hfe knockdown cells revealed alterations in the expression of several iron-associated genes, suggesting global disruption of intracellular iron homeostasis. Analyzing differentially expressed pathways further identified oxidative stress as the top pathway upregulated with Hfe loss. Enhanced 55Fe uptake and generation of reactive oxygen species (ROS) were found with Hfe knockdown, implicating toxic iron overload resulting in apoptotic cell death. Conclusions: Collectively, these findings identify a novel role for HFE in regulating iron homeostasis in GBM tumors and provide a potential avenue for future therapeutic development.

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Serine, glutamate, and proline in a high‐fat diet exacerbated metabolite reduction‐induced memory and cognitive decline

et al. 2023

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Epidemiological studies have shown that excessive consumption of meat may cause memory loss and cognitive decline, but the underlying mechanism is unknown. Here, a high‐chicken‐protein diet but not a high‐pork diet was found to have a markedly negative impact on the enteric nervous system and hippocampal function. Higher serine, glutamate, and proline levels in the high‐chicken‐protein diet inhibited the absorption capacity of amino acids, reduced the levels of neurotransmitters, and further increased hippocampal β‐secretase levels. Alzheimer's disease mouse model and cell studies confirmed that high‐chicken diet‐induced changes in the intestinal function further resulted in metabolic disorders with a reduction in L‐serine and niacinamide in serum, accumulation of hippocampal β‐amyloid, and eventually aggravated memory and cognitive decline. Our findings highlight the importance of serine, glutamate, and proline as systemic mediators of diet–gut–brain axis homeostasis against memory and cognitive dysfunctions associated with excessive intake of chicken.

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Severe consequences of a high-lipid diet include hydrogen sulfide dysfunction and enhanced aggression in glioblastoma

Abstract: Consumption of a high-fat diet (HFD) accelerates glioblastoma (GBM) by inhibiting the production and signaling of the tumor-suppressive metabolite hydrogen sulfide (H2S).

Cited by 41 publications

References 65 publications

Emerging roles of cystathionine β-synthase in various forms of cancer

Emerging roles of cystathionine β-synthase in various forms of cancer

Tumor cell-intrinsic HFE drives glioblastoma growth

Serine, glutamate, and proline in a high‐fat diet exacerbated metabolite reduction‐induced memory and cognitive decline

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