UMMS Affiliation
Program in Molecular Medicine
Publication Date
2013-10-17
Document Type
Article
Subjects
Adipose Tissue; Animals; Disease Models, Animal; Humans; Insulin Resistance; Mice; Tumor Necrosis Factor-alpha
Disciplines
Biochemistry | Cell Biology | Cellular and Molecular Physiology | Molecular Biology
Abstract
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-alpha, hypoxia, dexamethasone, high insulin, and a combination of TNF-alpha 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-alpha 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-alpha-induced insulin resistance, and we found that C/EPBbeta is a potential key regulator of adipose insulin resistance.
Rights and Permissions
This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-No Derivative Works License, which permits non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI of Published Version
10.1016/j.celrep.2013.08.039
Source
Cell Rep. 2013 Oct 17;5(1):259-70. doi: 10.1016/j.celrep.2013.08.039. Epub 2013 Oct 3. Link to article on publisher's site
Journal/Book/Conference Title
Cell reports
Related Resources
PubMed ID
24095730
Repository Citation
Lo, Kinyui Alice; Labadorf, Adam; Kennedy, Norman J.; Han, Myoung Souk; Yap, Yoon Sing; Matthews, Bryan; Xin, Xiaofeng; Sun, Lei; Davis, Roger J.; Lodish, Harvey F.; and Fraenkel, Ernest, "Analysis of in vitro insulin-resistance models and their physiological relevance to in vivo diet-induced adipose insulin resistance" (2013). Davis Lab Publications. 47.
https://escholarship.umassmed.edu/davis/47
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.
Included in
Biochemistry Commons, Cell Biology Commons, Cellular and Molecular Physiology Commons, Molecular Biology Commons