UMass Chan Medical School Faculty Publications

UMMS Affiliation

Program in Molecular Medicine; Davis Lab; UMass Metabolic Network

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Cellular and Molecular Physiology | Computational Biology | Integrative Biology | Molecular Biology | Nutritional and Metabolic Diseases | Systems Biology


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.


computational biology, high-fat diet, insulin resistance, integrative modeling, obesity, omic data, systems biology

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Copyright 2017 The Author(s). This is an open access article under the CC BY-NC-ND license (

DOI of Published Version



Cell Rep. 2017 Dec 12;21(11):3317-3328. doi: 10.1016/j.celrep.2017.11.059. Link to article on publisher's site

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Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.