Untargeted metabolomics reveals the inhibition effect of a high-fat diet on colorectal cancer tumorigenesis in obesity-resistant mice via regulating bile acid, glutathione, and glycerophospholipid metabolisms†

IF 5.1 1区 农林科学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Food & Function Pub Date : 2025-06-17 DOI:10.1039/D4FO06132B
Qi Cheng, Kun Na, Chunsheng Xu, He Peng, Xiaojian Lin, Jiajun Chen, Yan Li, Die Wu, Menghao Du and Xingya Wang
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引用次数: 0

Abstract

The interplay between high fat intake and cancer is complex and multifaceted. Contradictory results exist between obesity, high-fat diet (HFD), and colorectal cancer (CRC), necessitating further research. In this study, we investigated the effect of HFD on tumorigenesis in obesity-resistant and obesity-susceptible mouse models. Our results revealed that HFD significantly inhibited CRC HCT116 and HT-29 xenograft tumor growth in obesity-resistant BALB/c nude mice in comparison with a low-fat diet (LFD). HFD feeding did not induce increases in body weight, serum pro-inflammatory cytokines, and lipid accumulation in the liver and white adipose tissue (WAT) in nude mice. However, HFD promoted tumor growth in melanoma B16-F10-bearing C57BL/6J mice, accompanied by obesity and increased pro-inflammatory cytokine levels. Untargeted metabolomics showed that HFD induced significantly changed metabolites in serum, tumor, and liver samples of the HCT116 xenograft model. In all samples, many glycerophospholipids (e.g. LysoPE (0:0/20:1) and LysoPC (16:1)) and bile acids (e.g. glycocholic acid and chenodeoxycholic acid) were significantly reduced by HFD. Enrichment and pathway analyses suggested that bile acid biosynthesis and metabolisms of lipids, amino acids, and organic acids were significantly regulated by HFD. Additionally, the glutathione metabolism was significantly downregulated, while the TCA cycle was upregulated by HFD in tumor samples. Moreover, univariate and multivariate analyses on the differential metabolites in tumors suggested that uracil, chenodeoxycholic acid, glutathione, LysoPE (0:0/20:1), and SM (d18:1/18:0) were the main metabolite biomarkers for discrimination between LFD- and HFD-fed xenograft tumors. These findings suggest that HFD elicits an anti-tumorigenic effect against CRC in obesity-resistant BALB/c nude mice via regulating bile acid, glutathione, and glycerophospholipid metabolisms.

Abstract Image

非靶向代谢组学揭示了高脂肪饮食通过调节胆汁酸、谷胱甘肽和甘油磷脂代谢对肥胖抵抗小鼠结直肠癌肿瘤发生的抑制作用。
高脂肪摄入和癌症之间的相互作用是复杂和多方面的。肥胖、高脂饮食(high-fat diet, HFD)与结直肠癌(colorectal cancer, CRC)之间存在矛盾的结果,需要进一步的研究。在这项研究中,我们研究了HFD对肥胖抵抗和肥胖易感小鼠模型肿瘤发生的影响。我们的研究结果显示,与低脂饮食(LFD)相比,HFD显著抑制肥胖抵抗BALB/c裸鼠CRC HCT116和HT-29异种移植肿瘤的生长。饲喂高脂饲料不会导致裸鼠体重、血清促炎细胞因子以及肝脏和白色脂肪组织(WAT)的脂质积累增加。然而,HFD促进了携带b16 - f10的黑色素瘤小鼠C57BL/6J的肿瘤生长,并伴有肥胖和促炎细胞因子水平升高。非靶向代谢组学显示,HFD诱导HCT116异种移植模型的血清、肿瘤和肝脏样品中的代谢物发生显著变化。在所有样品中,HFD显著降低了许多甘油磷脂(如LysoPE(0:0/20:1)和LysoPC(16:1))和胆汁酸(如糖胆酸和鹅去氧胆酸)。富集和途径分析表明,HFD显著调节了胆汁酸的生物合成和脂质、氨基酸和有机酸的代谢。此外,肿瘤样品中谷胱甘肽代谢显著下调,而TCA循环被HFD上调。此外,对肿瘤差异代谢物的单因素和多因素分析表明,尿嘧啶、鹅去氧胆酸、谷胱甘肽、LysoPE(0:0/20:1)和SM (d18:1/18:0)是区分LFD和hfd喂养的异种移植肿瘤的主要代谢物生物标志物。这些发现表明,HFD通过调节胆酸、谷胱甘肽和甘油磷脂代谢,对肥胖抵抗型BALB/c裸鼠的结直肠癌具有抗肿瘤作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Food & Function
Food & Function BIOCHEMISTRY & MOLECULAR BIOLOGY-FOOD SCIENCE & TECHNOLOGY
CiteScore
10.10
自引率
6.60%
发文量
957
审稿时长
1.8 months
期刊介绍: Food & Function provides a unique venue for physicists, chemists, biochemists, nutritionists and other food scientists to publish work at the interface of the chemistry, physics and biology of food. The journal focuses on food and the functions of food in relation to health.
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