University of Massachusetts Medical School Faculty Publications
UMMS Affiliation
Program in Molecular Medicine; Davis Lab; UMass Metabolic Network
Publication Date
2017-12-12
Document Type
Article
Disciplines
Cellular and Molecular Physiology | Computational Biology | Integrative Biology | Molecular Biology | Nutritional and Metabolic Diseases | Systems Biology
Abstract
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.
Keywords
computational biology, high-fat diet, insulin resistance, integrative modeling, obesity, omic data, systems biology
Rights and Permissions
Copyright 2017 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
DOI of Published Version
10.1016/j.celrep.2017.11.059
Source
Cell Rep. 2017 Dec 12;21(11):3317-3328. doi: 10.1016/j.celrep.2017.11.059. Link to article on publisher's site
Related Resources
Journal/Book/Conference Title
Cell reports
PubMed ID
29241556
Repository Citation
Soltis, Anthony R.; Kennedy, Norman J.; Xin, Xiaofeng; Zhou, Feng; Ficarro, Scott B.; Yap, Yoon Sing; Matthews, Bryan J.; Lauffenburger, Douglas A.; White, Forest M.; Marto, Jarrod A.; Davis, Roger J.; and Fraenkel, Ernest, "Hepatic Dysfunction Caused by Consumption of a High-Fat Diet" (2017). University of Massachusetts Medical School Faculty Publications. 1475.
https://escholarship.umassmed.edu/faculty_pubs/1475
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Included in
Cellular and Molecular Physiology Commons, Computational Biology Commons, Integrative Biology Commons, Molecular Biology Commons, Nutritional and Metabolic Diseases Commons, Systems Biology Commons