期刊
CELL
卷 158, 期 6, 页码 1415-1430出版社
CELL PRESS
DOI: 10.1016/j.cell.2014.07.039
关键词
-
资金
- GlaxoSmithKline
- Faculty of Biology and Medicine of Lausanne
- Swiss National Science Foundation (SNSF) [33CSCO-122661]
- ERC (Proteomics v3.0) [AdG-233226]
- Fondation Romande pour la Recherche sur le Diabete
- EPFL
- ETHZ
- ERC [AdG-231138, AdG-233226)]
- Velux Stiftung
- LiverX
- AgingX programs of the Swiss Initiative for Systems Biology [51RTP0-151019, 2013/153]
- SNSF [31003A-140780, 31003A-143914, 3100A0-107679, CSRII3-136201]
- NIH [R01AG043930]
The manner by which genotype and environment affect complex phenotypes is one of the fundamental questions in biology. In this study, we quantified the transcriptome-a subset of the metabolome-and, using targeted proteomics, quantified a subset of the liver proteome from 40 strains of the BXD mouse genetic reference population on two diverse diets. We discovered dozens of transcript, protein, and metabolite QTLs, several of which linked to metabolic phenotypes. Most prominently, Dhtkd1 was identified as a primary regulator of 2-aminoadipate, explaining variance in fasted glucose and diabetes status in both mice and humans. These integrated molecular profiles also allowed further characterization of complex pathways, particularly the mitochondrial unfolded protein response (UPRmt). UPRmt shows strikingly variant responses at the transcript and protein level that are remarkably conserved among C. elegans, mice, and humans. Overall, these examples demonstrate the value of an integrated multilayered omics approach to characterize complex metabolic phenotypes.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据