Hepatic Dysfunction Caused by Consumption of a High-Fat Diet.
Hepatic Dysfunction Caused by Consumption of a High-Fat Diet.
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DOI：
10.1016/j.celrep.2017.11.059
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发表时间：
2017-12-12
期刊：
影响因子：
8.8
通讯作者：
Fraenkel E
中科院分区：
文献类型：
--
作者：
Soltis AR;Kennedy NJ;Xin X;Zhou F;Ficarro SB;Yap YS;Matthews BJ;Lauffenburger DA;White FM;Marto JA;Davis RJ;Fraenkel E
Obesity is a major human health crisis that promotes insulin resistance and, ultimately, type 2 diabetes. The molecular mechanisms that mediate this response occur across many highly complex biological regulatory levels that are incompletely understood. Here, we present a comprehensive molecular systems biology study of hepatic responses to high-fat feeding in mice. We interrogated diet-induced epigenomic, transcriptomic, proteomic, and metabolomic alterations using high-throughput omic methods and used a network modeling approach to integrate these diverse molecular signals. Our model indicated that disruption of hepatic architecture and enhanced hepatocyte apoptosis are among the numerous biological processes that contribute to early liver dysfunction and low-grade inflammation during the development of diet-induced metabolic syndrome. We validated these model findings with additional experiments on mouse liver sections. In total, we present an integrative systems biology study of diet-induced hepatic insulin resistance that uncovered molecular features promoting the development and maintenance of metabolic disease.
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影响因子：
7.7
作者：
Kang L;Lantier L;Kennedy A;Bonner JS;Mayes WH;Bracy DP;Bookbinder LH;Hasty AH;Thompson CB;Wasserman DH
通讯作者：
Wasserman DH
影响因子：
3.5
作者：
Choe, Chi-un;Nabuurs, Christine;Isbrandt, Dirk
通讯作者：
Isbrandt, Dirk
影响因子：
--
作者：
Langmead, Ben
通讯作者：
Langmead, Ben
影响因子：
12.3
作者：
Carpenter AE;Jones TR;Lamprecht MR;Clarke C;Kang IH;Friman O;Guertin DA;Chang JH;Lindquist RA;Moffat J;Golland P;Sabatini DM
通讯作者：
Sabatini DM
影响因子：
64.8
作者：
Kahn, Steven E.;Hull, Rebecca L.;Utzschneider, Kristina M.
通讯作者：
Utzschneider, Kristina M.