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| Status |
Public on Sep 14, 2018 |
| Title |
Antiretroviral therapy potentiates high-fat diet induced obesity and glucose intolerance |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Background Breakthroughs in HIV treatment, especially antiretroviral therapy (ART), have massively reduced mortality. However, ART-treated individuals display elevated rates of obesity, diabetes, and cardiovascular disease, collectively known as metabolic syndrome. These co-morbidities represent a considerable threat to long-term survival and quality of life. Previous studies have shown that high-fat feeding induces persistent low-grade systemic and adipose tissue inflammation contributing to insulin resistance and metabolic dysregulation via adipose-infiltrating macrophages.
Methods and Results Studies herein test the hypothesis that ART potentiates the inflammatory effects of a high-fat diet (HFD). C57Bl/6J mice on a HFD or standard chow containing ART or vehicle, were subjected to functional metabolic testing, RNA-sequencing of epididymal white adipose tissue (eWAT), and array-based kinomic analysis of eWAT-infiltrating macrophages. ART-treated mice on a HFD displayed fat mass accumulation, impaired glucose tolerance, and potentiated insulin resistance. Gene set enrichment and kinomic array analyses revealed a pro-inflammatory transcriptional signature depicting granulocyte migration and activation.
Conclusions The current study reveals a HFD-ART interaction that increases inflammatory transcriptional pathways in eWAT consistent with macrophage infiltration, resulting in impaired glucose metabolism, energy balance, and metabolic dysfunction.
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| Overall design |
RNA sequencing analysis of mice given high-fat diet or standard chow diet with/without Atripla (Efavirenz, Emtricidabine, and Tenofovir disoproxil fumarate) for 80 days
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| Web link |
https://www.sciencedirect.com/science/article/pii/S2212877818302321?via%3Dihub
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| Contributor(s) |
Pepin ME, Habegger KM, Tse H, Wende AR |
| Citation(s) |
29731256 |
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| Submission date |
Feb 01, 2018 |
| Last update date |
Mar 21, 2019 |
| Contact name |
Mark Emile Pepin |
| E-mail(s) |
pepinme@gmail.com
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| Organization name |
University of Alabama at Birmingham
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| Department |
Biomedical Engineering
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| Lab |
Adam Wende Laboratory
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| Street address |
1825 University Blvd
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| City |
Birmingham |
| State/province |
AL |
| ZIP/Postal code |
35294-2182 |
| Country |
USA |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA432595 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE110035_countData_EWAT.txt.gz |
316.8 Kb |
(ftp)(http) |
TXT |
| Raw data are available in SRA |
| Processed data are available on Series record |
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