Analysis of In Vitro Insulin-Resistance Models and Their Physiological Relevance to In Vivo Diet-Induced Adipose Insulin Resistance
Diet-induced obesity (DIO) predisposes individuals to insulin resistance, and adipose tissue has a major role in the disease. Insulin resistance can be induced in cultured adipocytes by a variety of treatments, but what aspects of the in vivo responses are captured by these models remains unknown. W...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Elsevier
2014
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| Online Access: | http://hdl.handle.net/1721.1/90558 https://orcid.org/0000-0002-7029-7415 https://orcid.org/0000-0001-9249-8181 https://orcid.org/0000-0002-6804-251X |
| _version_ | 1810985766707265536 |
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| author | Lo, Kinyui Alice Labadorf, Adam Kennedy, Norman J. Han, Myoung Sook Yap, Yoon Sing Matthews, Bryan Xin, Xiaofeng Sun, Lei Davis, Roger J. Lodish, Harvey F. Fraenkel, Ernest |
| author2 | Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory |
| author_facet | Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory Lo, Kinyui Alice Labadorf, Adam Kennedy, Norman J. Han, Myoung Sook Yap, Yoon Sing Matthews, Bryan Xin, Xiaofeng Sun, Lei Davis, Roger J. Lodish, Harvey F. Fraenkel, Ernest |
| author_sort | Lo, Kinyui Alice |
| collection | MIT |
| description | Diet-induced obesity (DIO) predisposes individuals to insulin resistance, and adipose tissue has a major role in the disease. Insulin resistance can be induced in cultured adipocytes by a variety of treatments, but what aspects of the in vivo responses are captured by these models remains unknown. We use global RNA sequencing to investigate changes induced by TNF-α, hypoxia, dexamethasone, high insulin, and a combination of TNF-α and hypoxia, comparing the results to the changes in white adipose tissue from DIO mice. We found that different in vitro models capture distinct features of DIO adipose insulin resistance, and a combined treatment of TNF-α and hypoxia is most able to mimic the in vivo changes. Using genome-wide DNase I hypersensitivity followed by sequencing, we further examined the transcriptional regulation of TNF-α-induced insulin resistance, and we found that C/EPBβ is a potential key regulator of adipose insulin resistance. |
| first_indexed | 2024-09-23T11:23:33Z |
| format | Article |
| id | mit-1721.1/90558 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:23:33Z |
| publishDate | 2014 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/905582022-10-01T03:17:17Z Analysis of In Vitro Insulin-Resistance Models and Their Physiological Relevance to In Vivo Diet-Induced Adipose Insulin Resistance Lo, Kinyui Alice Labadorf, Adam Kennedy, Norman J. Han, Myoung Sook Yap, Yoon Sing Matthews, Bryan Xin, Xiaofeng Sun, Lei Davis, Roger J. Lodish, Harvey F. Fraenkel, Ernest Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research Lo, Kinyui Alice Labadorf, Adam Yap, Yoon Sing Matthews, Bryan Xin, Xiaofeng Lodish, Harvey F. Fraenkel, Ernest Diet-induced obesity (DIO) predisposes individuals to insulin resistance, and adipose tissue has a major role in the disease. Insulin resistance can be induced in cultured adipocytes by a variety of treatments, but what aspects of the in vivo responses are captured by these models remains unknown. We use global RNA sequencing to investigate changes induced by TNF-α, hypoxia, dexamethasone, high insulin, and a combination of TNF-α and hypoxia, comparing the results to the changes in white adipose tissue from DIO mice. We found that different in vitro models capture distinct features of DIO adipose insulin resistance, and a combined treatment of TNF-α and hypoxia is most able to mimic the in vivo changes. Using genome-wide DNase I hypersensitivity followed by sequencing, we further examined the transcriptional regulation of TNF-α-induced insulin resistance, and we found that C/EPBβ is a potential key regulator of adipose insulin resistance. National Institutes of Health (U.S.) (Grant DK-068348) National Institutes of Health (U.S.) (Grant R24 DK-090963) National Institutes of Health (U.S.) (Grant R01GM-089903) 2014-10-02T18:58:25Z 2014-10-02T18:58:25Z 2013-10 2013-07 Article http://purl.org/eprint/type/JournalArticle 22111247 http://hdl.handle.net/1721.1/90558 Lo, Kinyui Alice, Adam Labadorf, Norman J. Kennedy, Myoung Sook Han, Yoon Sing Yap, Bryan Matthews, Xiaofeng Xin, et al. “Analysis of In Vitro Insulin-Resistance Models and Their Physiological Relevance to In Vivo Diet-Induced Adipose Insulin Resistance.” Cell Reports 5, no. 1 (October 2013): 259–270. https://orcid.org/0000-0002-7029-7415 https://orcid.org/0000-0001-9249-8181 https://orcid.org/0000-0002-6804-251X en_US http://dx.doi.org/10.1016/j.celrep.2013.08.039 Cell Reports Creative Commons Attribution http://creativecommons.org/licenses/by-nc-nd/3.0/ application/pdf Elsevier Elsevier |
| spellingShingle | Lo, Kinyui Alice Labadorf, Adam Kennedy, Norman J. Han, Myoung Sook Yap, Yoon Sing Matthews, Bryan Xin, Xiaofeng Sun, Lei Davis, Roger J. Lodish, Harvey F. Fraenkel, Ernest Analysis of In Vitro Insulin-Resistance Models and Their Physiological Relevance to In Vivo Diet-Induced Adipose Insulin Resistance |
| title | Analysis of In Vitro Insulin-Resistance Models and Their Physiological Relevance to In Vivo Diet-Induced Adipose Insulin Resistance |
| title_full | Analysis of In Vitro Insulin-Resistance Models and Their Physiological Relevance to In Vivo Diet-Induced Adipose Insulin Resistance |
| title_fullStr | Analysis of In Vitro Insulin-Resistance Models and Their Physiological Relevance to In Vivo Diet-Induced Adipose Insulin Resistance |
| title_full_unstemmed | Analysis of In Vitro Insulin-Resistance Models and Their Physiological Relevance to In Vivo Diet-Induced Adipose Insulin Resistance |
| title_short | Analysis of In Vitro Insulin-Resistance Models and Their Physiological Relevance to In Vivo Diet-Induced Adipose Insulin Resistance |
| title_sort | analysis of in vitro insulin resistance models and their physiological relevance to in vivo diet induced adipose insulin resistance |
| url | http://hdl.handle.net/1721.1/90558 https://orcid.org/0000-0002-7029-7415 https://orcid.org/0000-0001-9249-8181 https://orcid.org/0000-0002-6804-251X |
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