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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
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Elsevier
2018
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| Online Access: | http://hdl.handle.net/1721.1/113269 https://orcid.org/0000-0002-6804-251X https://orcid.org/0000-0002-1545-1651 https://orcid.org/0000-0001-9249-8181 |
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| author | Kennedy, Norman J. Zhou, Feng Ficarro, Scott B. Marto, Jarrod A. Davis, Roger J. Soltis, Anthony Robert Xin, Xiaofeng Yap, Yoon Sing Matthews, Bryan Lauffenburger, Douglas A White, Forest M Fraenkel, Ernest |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Kennedy, Norman J. Zhou, Feng Ficarro, Scott B. Marto, Jarrod A. Davis, Roger J. Soltis, Anthony Robert Xin, Xiaofeng Yap, Yoon Sing Matthews, Bryan Lauffenburger, Douglas A White, Forest M Fraenkel, Ernest |
| author_sort | Kennedy, Norman J. |
| collection | MIT |
| 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. Soltis et al. performed a systems biology study of obesity-induced hepatic insulin resistance in mice. They collected a variety of omic datasets, including metabolomics, and integrated these into a network model. They tested model predictions and identified widespread hepatocellular injury and enhanced hepatocyte apoptosis as features of hepatic insulin resistance. Keywords: insulin resistance; high-fat diet; obesity; systems biology; computational biology;
integrative modeling; omic data |
| first_indexed | 2024-09-23T09:06:47Z |
| format | Article |
| id | mit-1721.1/113269 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T09:06:47Z |
| publishDate | 2018 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1132692022-09-26T10:33:30Z Hepatic Dysfunction Caused by Consumption of a High-Fat Diet Kennedy, Norman J. Zhou, Feng Ficarro, Scott B. Marto, Jarrod A. Davis, Roger J. Soltis, Anthony Robert Xin, Xiaofeng Yap, Yoon Sing Matthews, Bryan Lauffenburger, Douglas A White, Forest M Fraenkel, Ernest Massachusetts Institute of Technology. Department of Biological Engineering Soltis, Anthony Robert Xin, Xiaofeng Yap, Yoon Sing Matthews, Bryan Lauffenburger, Douglas A White, Forest M Fraenkel, Ernest 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. Soltis et al. performed a systems biology study of obesity-induced hepatic insulin resistance in mice. They collected a variety of omic datasets, including metabolomics, and integrated these into a network model. They tested model predictions and identified widespread hepatocellular injury and enhanced hepatocyte apoptosis as features of hepatic insulin resistance. Keywords: insulin resistance; high-fat diet; obesity; systems biology; computational biology; integrative modeling; omic data National Institutes of Health (U.S.) (Grant R24 DK-090963) National Institutes of Health (U.S.) (Grant R01 NS-089076) National Science Foundation (U.S.) (Award DB1-0821391) National Institutes of Health (U.S.) (Grant P30-ES002109) 2018-01-22T21:03:38Z 2018-01-22T21:03:38Z 2017-12 2017-11 2018-01-19T19:25:11Z Article http://purl.org/eprint/type/JournalArticle 2211-1247 http://hdl.handle.net/1721.1/113269 Soltis, Anthony R. et al. “Hepatic Dysfunction Caused by Consumption of a High-Fat Diet.” Cell Reports 21, 11 (December 2017): 3317–3328 © 2017 The Author(s) https://orcid.org/0000-0002-6804-251X https://orcid.org/0000-0002-1545-1651 https://orcid.org/0000-0001-9249-8181 http://dx.doi.org/10.1016/j.celrep.2017.11.059 Cell Reports Attribution-NonCommercial-NoDerivatives 4.0 International https://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier Cell Reports |
| spellingShingle | Kennedy, Norman J. Zhou, Feng Ficarro, Scott B. Marto, Jarrod A. Davis, Roger J. Soltis, Anthony Robert Xin, Xiaofeng Yap, Yoon Sing Matthews, Bryan Lauffenburger, Douglas A White, Forest M Fraenkel, Ernest Hepatic Dysfunction Caused by Consumption of a High-Fat Diet |
| title | 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_short | Hepatic Dysfunction Caused by Consumption of a High-Fat Diet |
| title_sort | hepatic dysfunction caused by consumption of a high fat diet |
| url | http://hdl.handle.net/1721.1/113269 https://orcid.org/0000-0002-6804-251X https://orcid.org/0000-0002-1545-1651 https://orcid.org/0000-0001-9249-8181 |
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