Medical Systems Biology Group, Lübeck Institute for Experimental Dermatology, University of Lübeck, 23562 Lübeck, Germany.
Institute for Cardiogenetics, University of Lübeck, 23562 Lübeck, Germany.
Cells. 2021 May 23;10(6):1292. doi: 10.3390/cells10061292.
CYP17A1 is a cytochrome P450 enzyme that has 17-alpha-hydroxylase and C17,20-lyase activities. deficiency is associated with high body mass and visceral fat deposition in atherosclerotic female ApoE knockout (KO, d/d or -/-) mice. In the present study, we aimed to investigate the effects of diet and genotype on the gut microbiome. Female (d/d) × ApoE (d/d) (DKO) and ApoE (d/d) (controls) were fed either standard chow or a Western-type diet (WTD), and we demonstrated the effects of genetics and diet on the body mass of the mice and composition of their gut microbiome. We found a significantly lower alpha diversity after accounting for the ecological network structure in DKO mice and WTD-fed mice compared with chow-fed ApoE(d/d). Furthermore, we found a strong significant positive association of the vs. ratio with body mass and the circulating total cholesterol and triglyceride concentrations of the mice when feeding the WTD, independent of the genotype. Further pathway enrichment and network analyses revealed a substantial effect of genotype on associated cardiovascular and obesity-related pathways involving aspartate and L-arginine. Future studies are required to validate these findings and further investigate the role of aspartate/L-arginine pathways in the obesity and body fat distribution in our mouse model.
CYP17A1 是一种细胞色素 P450 酶,具有 17-α羟化酶和 C17、20-裂解酶活性。缺陷与动脉粥样硬化雌性 ApoE 敲除(KO,d/d 或-/-)小鼠的高体重和内脏脂肪沉积有关。在本研究中,我们旨在研究饮食和基因型对肠道微生物组的影响。雌性(d/d)×ApoE(d/d)(DKO)和 ApoE(d/d)(对照)分别喂食标准饲料或西式饮食(WTD),我们证明了遗传和饮食对小鼠体重和肠道微生物组组成的影响。我们发现,在考虑到生态网络结构后,DKO 小鼠和 WTD 喂养小鼠的α多样性明显低于喂食标准饲料的 ApoE(d/d)。此外,当喂食 WTD 时,我们发现与 17-β-羟类固醇脱氢酶 1 型()与体重以及小鼠循环总胆固醇和甘油三酯浓度之间存在强烈的正相关,而与基因型无关。进一步的途径富集和网络分析表明,基因型对涉及天冬氨酸和 L-精氨酸的心血管和肥胖相关途径有显著影响。需要进一步的研究来验证这些发现,并进一步研究天冬氨酸/L-精氨酸途径在我们的小鼠模型中的肥胖和体脂肪分布中的作用。