Everett Jeremy R, Karpe Fredrik, Le Guennec Adrien, Neville Matt, Redfield Christina
Medway Metabonomics Research Group, University of Greenwich, Chatham Maritime, Kent, ME4 4TB, UK.
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, OX3 7LE, UK.
Metabolomics. 2025 Sep 9;21(5):135. doi: 10.1007/s11306-025-02308-1.
Knockout of the Fmo5 gene in mice led to a lean, slow-ageing phenotype characterised by the presence of 2,3-butanediol isomers in their urine and plasma. Oral treatment of wildtype mice with 2,3-butanediol led to a low cholesterol, low epididymal fat phenotype.
Determine if significant, heterozygous coding variations in human FMO5 would give rise to similar clinical and metabolic phenotypes in humans, as in C57BL/6J mice with knockout of the Fmo5 gene and in particular, increased excretion of 2,3-butanediol.
Recruitment of 12 female, Oxford Biobank volunteers with heterozygous coding variations in FMO5, associated with changed clinical traits, and 12 age- and gender-matched controls. Analysis of the key NMR-based, urine and plasma, metabolic phenotypes of these volunteers to determine if there were any statistically significant differences.
Some clinical parameters of the female volunteers with heterozygous coding variations in FMO5 were altered in a direction consistent with our hypothesis viz; lower insulin levels and lower waist circumference, but no consistent elevation of urinary 2,3-butanediol was found in the subjects with heterozygous coding variations in FMO5.
Heterozygous coding variations in human FMO5 appeared to have some impact on the clinical phenotype of the females in this study but the natural variation in the levels of 2,3-butanediol was higher than any inter-group differences between women with heterozygous coding variations in human FMO5 and the women in the control group with wildtype FMO5.
敲除小鼠的Fmo5基因会导致一种瘦型、衰老缓慢的表型，其特征是尿液和血浆中存在2,3 - 丁二醇异构体。用2,3 - 丁二醇对野生型小鼠进行口服治疗会导致低胆固醇、低附睾脂肪表型。
确定人类FMO5中显著的杂合编码变异是否会在人类中产生与Fmo5基因敲除的C57BL/6J小鼠类似的临床和代谢表型，特别是2,3 - 丁二醇排泄增加。
招募12名具有与临床特征改变相关的FMO5杂合编码变异的女性牛津生物银行志愿者，以及12名年龄和性别匹配的对照。分析这些志愿者基于核磁共振的关键尿液和血浆代谢表型，以确定是否存在任何统计学上的显著差异。
FMO5具有杂合编码变异的女性志愿者的一些临床参数朝着与我们的假设一致的方向改变，即胰岛素水平较低和腰围较小，但在FMO5具有杂合编码变异的受试者中未发现尿中2,3 - 丁二醇持续升高。
人类FMO5中的杂合编码变异似乎对本研究中的女性临床表型有一定影响，但2,3 - 丁二醇水平的自然变异高于人类FMO5具有杂合编码变异的女性与野生型FMO5对照组女性之间的任何组间差异。
