Zeng Huawei, Umar Shahid, Liu Zhenhua, Bukowski Michael R
Grand Forks Human Nutrition Research Center, Agricultural Research Service, United States Department of Agriculture, Grand Forks, ND 58203, USA.
Department of Surgery and University of Kansas Cancer Center, Kansas City, KS 66160, USA.
Metabolites. 2021 Jul 9;11(7):448. doi: 10.3390/metabo11070448.
Consumption of a high-fat diet (HFD) links obesity to colon cancer in humans. Our data show that a HFD (45% energy fat versus 16% energy fat in an AIN-93 diet (AIN)) promotes azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) formation in a mouse cancer model. However, the underlying metabolic basis remains to be determined. In the present study, we hypothesize that AOM treatment results in different plasma metabolomic responses in diet-induced obese mice. An untargeted metabolomic analysis was performed on the plasma samples by gas chromatography time-of-flight mass spectrometry (GC-TOF-MS). We found that 53 of 144 identified metabolites were different between the 4 groups of mice (AIN, AIN + AOM, HFD, HFD + AOM), and sparse partial least-squares discriminant analysis showed a separation between the HFD and HFD + AOM groups but not the AIN and AIN + AOM groups. Moreover, the concentrations of dihydrocholesterol and cholesterol were inversely associated with AOM-induced colonic ACF formation. Functional pathway analyses indicated that diets and AOM-induced colonic ACF modulated five metabolic pathways. Collectively, in addition to differential plasma metabolomic responses, AOM treatment decreases dihydrocholesterol and cholesterol levels and alters the composition of plasma metabolome to a greater extent in mice fed a HFD compared to the AIN.
食用高脂肪饮食（HFD）会导致人类肥胖与结肠癌相关联。我们的数据表明，在小鼠癌症模型中，HFD（占能量的45%脂肪，而AIN-93饮食（AIN）中占能量的16%脂肪）会促进由氧化偶氮甲烷（AOM）诱导的结肠异常隐窝病灶（ACF）形成。然而，其潜在的代谢基础仍有待确定。在本研究中，我们假设AOM处理会导致饮食诱导的肥胖小鼠出现不同的血浆代谢组学反应。通过气相色谱飞行时间质谱（GC-TOF-MS）对血浆样本进行了非靶向代谢组学分析。我们发现，在4组小鼠（AIN、AIN + AOM、HFD、HFD + AOM）中，144种已鉴定的代谢物中有53种存在差异，稀疏偏最小二乘判别分析显示HFD组和HFD + AOM组之间有区分，但AIN组和AIN + AOM组之间没有。此外，二氢胆固醇和胆固醇的浓度与AOM诱导的结肠ACF形成呈负相关。功能通路分析表明，饮食和AOM诱导的结肠ACF调节了五条代谢通路。总体而言，除了不同的血浆代谢组学反应外，与AIN组相比，AOM处理会降低喂食HFD小鼠的二氢胆固醇和胆固醇水平，并在更大程度上改变血浆代谢组的组成。
