Oleic Acid and Insulin as Key Characteristics of T2D Promote Colorectal Cancer Deterioration in Xenograft Mice Revealed by Functional Metabolomics

Zhang, Ying; Wang, Di; Lv, Bo; Hou, Xiaoying; Liu, Qiwei; Liao, Chuyao; Xu, Rong; Zhang, Yuxin; Xu, Fengguo; Zhang, Pei

doi:10.3389/fonc.2021.685059

Cited by 10 publications

(8 citation statements)

References 52 publications

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“…To examine the connection between fecal and plasma fatty acids, correlation analysis ( Figure 4 ) was used to show that only the concentrations of linoleic acid and oleic acid in the fecal samples were positively associated with concentrations in the plasma samples. These findings are in line with recent reports that dietary linoleic acid and oleic acid are unsaturated fatty acids known to cause inflammation and promote the development of colon cancer [ 24 , 25 , 26 , 27 ].…”

Section: Discussionsupporting

confidence: 92%

Changes in the Fecal Metabolome Accompany an Increase in Aberrant Crypt Foci in the Colon of C57BL/6 Mice Fed with a High-Fat Diet

et al. 2022

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High-fat diet (HFD)-induced obesity is a risk factor for colon cancer. Our previous data show that compared to an AIN-93 diet (AIN), a HFD promotes azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) formation and microbial dysbiosis in C57BL/6 mice. To explore the underlying metabolic basis, we hypothesize that AOM treatment triggers a different fecal metabolomic profile in C57BL/6 mice fed the HFD or the AIN. We found that 65 of 196 identified metabolites were significantly different among the four groups of mice (AIN, AIN + AOM, HFD, and HFD + AOM). A sparse partial least squares discriminant analysis (sPLSDA) showed that concentrations of nine fecal lipid metabolites were increased in the HFD + AOM compared to the HFD, which played a key role in overall metabolome group separation. These nine fecal lipid metabolite concentrations were positively associated with the number of colonic ACF, the cell proliferation of Ki67 proteins, and the abundance of dysbiotic bacteria. These data suggest that the process of AOM-induced ACF formation may increase selective fecal lipid concentrations in mice fed with a HFD but not an AIN. Collectively, the accumulation of these critical fecal lipid species may alter the overall metabolome during tumorigenesis in the colon.

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Section: Discussionsupporting

confidence: 92%

Changes in the Fecal Metabolome Accompany an Increase in Aberrant Crypt Foci in the Colon of C57BL/6 Mice Fed with a High-Fat Diet

et al. 2022

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“…Another study observed an association between oleic acid, the main monounsaturated fatty acid in bovine milk, and the gene MYC. It showed that oleic acid promotes colorectal cancer development by upregulation of MYC , among others [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

Pooled analysis of epigenome-wide association studies of food consumption in KORA, TwinsUK and LLS

et al. 2022

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Purpose Examining epigenetic patterns is a crucial step in identifying molecular changes of disease pathophysiology, with DNA methylation as the most accessible epigenetic measure. Diet is suggested to affect metabolism and health via epigenetic modifications. Thus, our aim was to explore the association between food consumption and DNA methylation. Methods Epigenome-wide association studies were conducted in three cohorts: KORA FF4, TwinsUK, and Leiden Longevity Study, and 37 dietary exposures were evaluated. Food group definition was harmonized across the three cohorts. DNA methylation was measured using Infinium MethylationEPIC BeadChip in KORA and Infinium HumanMethylation450 BeadChip in the Leiden study and the TwinsUK study. Overall, data from 2293 middle-aged men and women were included. A fixed-effects meta-analysis pooled study-specific estimates. The significance threshold was set at 0.05 for false-discovery rate-adjusted p values per food group. Results We identified significant associations between the methylation level of CpG sites and the consumption of onions and garlic (2), nuts and seeds (18), milk (1), cream (11), plant oils (4), butter (13), and alcoholic beverages (27). The signals targeted genes of metabolic health relevance, for example, GLI1, RPTOR, and DIO1, among others. Conclusion This EWAS is unique with its focus on food groups that are part of a Western diet. Significant findings were mostly related to food groups with a high-fat content.

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“…The relevance of exogenous FA and CD36-mediated metastasis was further supported by findings from Zhang et al, laboratory [ 64 ]. They described that oleic acid (OA) promotes metastasis and proliferation of colon carcinoma cells HCT116.…”

Section: Metabolic Reprogramming and Metastasismentioning

confidence: 64%

CD36-Fatty Acid-Mediated Metastasis via the Bidirectional Interactions of Cancer Cells and Macrophages

Zaidi

Shazali

Leow

et al. 2022

Cells

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Tumour heterogeneity refers to the complexity of cell subpopulations coexisting within the tumour microenvironment (TME), such as proliferating tumour cells, tumour stromal cells and infiltrating immune cells. The bidirectional interactions between cancer and the surrounding microenvironment mark the tumour survival and promotion functions, which allow the cancer cells to become invasive and initiate the metastatic cascade. Importantly, these interactions have been closely associated with metabolic reprogramming, which can modulate the differentiation and functions of immune cells and thus initiate the antitumour response. The purpose of this report is to review the CD36 receptor, a prominent cell receptor in metabolic activity specifically in fatty acid (FA) uptake, for the metabolic symbiosis of cancer–macrophage. In this review, we provide an update on metabolic communication between tumour cells and macrophages, as well as how the immunometabolism indirectly orchestrates the tumour metastasis.

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Oleic Acid and Insulin as Key Characteristics of T2D Promote Colorectal Cancer Deterioration in Xenograft Mice Revealed by Functional Metabolomics

Cited by 10 publications

References 52 publications

Changes in the Fecal Metabolome Accompany an Increase in Aberrant Crypt Foci in the Colon of C57BL/6 Mice Fed with a High-Fat Diet

Changes in the Fecal Metabolome Accompany an Increase in Aberrant Crypt Foci in the Colon of C57BL/6 Mice Fed with a High-Fat Diet

Pooled analysis of epigenome-wide association studies of food consumption in KORA, TwinsUK and LLS

CD36-Fatty Acid-Mediated Metastasis via the Bidirectional Interactions of Cancer Cells and Macrophages

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