C. elegans as a model for inter-individual variation in metabolism.
C. elegans as a model for inter-individual variation in metabolism.
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C. elegans作为代谢个体间差异的模型。
DOI：
10.1038/s41586-022-04951-3
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发表时间：
2022-07
期刊：
影响因子：
64.8
通讯作者：
中科院分区：
文献类型：
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作者：
个体可以表现出由遗传背景、营养输入、微生物群和其他环境因素的相互作用引起的代谢差异。由于饮食和生活方式的差异等原因，很难将代谢差异与基因组变异联系起来，并推导出人类的潜在分子机制。在这里，我们引入秀丽隐杆线虫作为模型来研究代谢的个体间差异。通过比较三种野生菌株和常用的N2实验室菌株，我们发现已知和以前未描述的代谢产物丰度的差异。新的代谢物包括3-羟基丙酸酯（3 HP）和几种氨基酸（3 HP-AA）之间的缀合物，这些氨基酸在一种野生菌株中丰度要高得多。3 HP是丙酸分流途径中的中间体，当通过经典的维生素B12依赖性丙酸分解途径的流量受到干扰时，3 HP被激活。我们证明，增加3 HP-AA积累是由HPHD-1，其中3 HP是一个底物的遗传变异。我们的研究结果表明，3 HP-AA生产代表了一个'分流内分流'的途径，以适应减少功能等位基因在hphd-1。这项研究为开发代谢网络模型提供了第一步，该模型可以捕获代谢的个体特异性差异，并更紧密地代表整个物种的多样性。
Individuals can exhibit differences in metabolism caused by the interplay of genetic background, nutritional input, microbiota, and other environmental factors. It is difficult to connect differences in metabolism to genomic variation and derive underlying molecular mechanisms in humans due to differences in diet and lifestyle, among others. Here, we introduce the nematode Caenorhabditis elegans as a model to study inter-individual variation in metabolism. By comparing three wild strains and the commonly used N2 laboratory strain, we find differences in the abundances of both known and previously undescribed metabolites. Novel metabolites include conjugates between 3-hydroxypropionate (3HP) and several amino acids (3HP-AAs) that are much higher in abundance in one of the wild strains. 3HP is an intermediate in the propionate shunt pathway, which is activated when flux through the canonical, vitamin B12-dependent propionate breakdown pathway is perturbed. We demonstrate that increased 3HP-AA accumulation is caused by genetic variation in HPHD-1, for which 3HP is a substrate. Our results suggest that 3HP-AA production represents a ‘shunt-within-a-shunt’ pathway to accommodate a reduction-of-function allele in hphd-1. This study provides a first step to developing metabolic network models that capture individual-specific differences of metabolism and more closely represent the diversity found in entire species.
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DOI：
10.1038/nrendo.2016.186
发表时间：
2017-03
期刊：
Nature reviews. Endocrinology
影响因子：
--
作者：
Braun JM
通讯作者：
Braun JM
影响因子：
8.6
作者：
Falcke JM;Bose N;Artyukhin AB;Rödelsperger C;Markov GV;Yim JJ;Grimm D;Claassen MH;Panda O;Baccile JA;Zhang YK;Le HH;Jolic D;Schroeder FC;Sommer RJ
通讯作者：
Sommer RJ
影响因子：
3.8
作者：
Boyd WA;McBride SJ;Rice JR;Snyder DW;Freedman JH
通讯作者：
Freedman JH
影响因子：
16.8
作者：
Lee D;Zdraljevic S;Stevens L;Wang Y;Tanny RE;Crombie TA;Cook DE;Webster AK;Chirakar R;Baugh LR;Sterken MG;Braendle C;Félix MA;Rockman MV;Andersen EC
通讯作者：
Andersen EC
DOI：
10.1038/s41576-021-00414-z
发表时间：
2022-03
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
Loos RJF;Yeo GSH
通讯作者：
Yeo GSH