Hepatic Dysfunction Caused by Consumption of a High-Fat Diet
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 sys...
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doaj-e5eebe857cdb4e9ab9c12f38a092d85a2020-11-24T21:21:03ZengElsevierCell Reports2211-12472017-12-0121113317332810.1016/j.celrep.2017.11.059Hepatic Dysfunction Caused by Consumption of a High-Fat DietAnthony R. Soltis0Norman J. Kennedy1Xiaofeng Xin2Feng Zhou3Scott B. Ficarro4Yoon Sing Yap5Bryan J. Matthews6Douglas A. Lauffenburger7Forest M. White8Jarrod A. Marto9Roger J. Davis10Ernest Fraenkel11Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USAProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USADepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USADepartment of Cancer Biology, Department of Oncologic Pathology, and Blais Proteomics Center, Dana-Farber Cancer Institute, Boston, MA 02215, USADepartment of Cancer Biology, Department of Oncologic Pathology, and Blais Proteomics Center, Dana-Farber Cancer Institute, Boston, MA 02215, USADepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USADepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USADepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USADepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USADepartment of Cancer Biology, Department of Oncologic Pathology, and Blais Proteomics Center, Dana-Farber Cancer Institute, Boston, MA 02215, USAProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USADepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USAObesity 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.http://www.sciencedirect.com/science/article/pii/S2211124717317114insulin resistancehigh-fat dietobesitysystems biologycomputational biologyintegrative modelingomic data |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Anthony R. Soltis Norman J. Kennedy Xiaofeng Xin Feng Zhou Scott B. Ficarro Yoon Sing Yap Bryan J. Matthews Douglas A. Lauffenburger Forest M. White Jarrod A. Marto Roger J. Davis Ernest Fraenkel |
spellingShingle |
Anthony R. Soltis Norman J. Kennedy Xiaofeng Xin Feng Zhou Scott B. Ficarro Yoon Sing Yap Bryan J. Matthews Douglas A. Lauffenburger Forest M. White Jarrod A. Marto Roger J. Davis Ernest Fraenkel Hepatic Dysfunction Caused by Consumption of a High-Fat Diet Cell Reports insulin resistance high-fat diet obesity systems biology computational biology integrative modeling omic data |
author_facet |
Anthony R. Soltis Norman J. Kennedy Xiaofeng Xin Feng Zhou Scott B. Ficarro Yoon Sing Yap Bryan J. Matthews Douglas A. Lauffenburger Forest M. White Jarrod A. Marto Roger J. Davis Ernest Fraenkel |
author_sort |
Anthony R. Soltis |
title |
Hepatic Dysfunction Caused by Consumption of a High-Fat Diet |
title_short |
Hepatic Dysfunction Caused by Consumption of a High-Fat Diet |
title_full |
Hepatic Dysfunction Caused by Consumption of a High-Fat Diet |
title_fullStr |
Hepatic Dysfunction Caused by Consumption of a High-Fat Diet |
title_full_unstemmed |
Hepatic Dysfunction Caused by Consumption of a High-Fat Diet |
title_sort |
hepatic dysfunction caused by consumption of a high-fat diet |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2017-12-01 |
description |
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. |
topic |
insulin resistance high-fat diet obesity systems biology computational biology integrative modeling omic data |
url |
http://www.sciencedirect.com/science/article/pii/S2211124717317114 |
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