| Title: | Increased body mass index is linked to systemic inflammation through altered chromatin co-accessibility in human preadipocytes |
| Journal: | Nature Communications |
| Published: | 14 Jul 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/37452040/ |
| DOI: | https://doi.org/10.1038/s41467-023-39919-y |
| URL: | https://www.nature.com/articles/s41467-023-39919-y.pdf |
Publication 11627
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Abstract
Obesity-induced adipose tissue dysfunction can cause low-grade inflammation and downstream obesity comorbidities. Although preadipocytes may contribute to this pro-inflammatory environment, the underlying mechanisms are unclear. We used human primary preadipocytes from body mass index (BMI) -discordant monozygotic (MZ) twin pairs to generate epigenetic (ATAC-sequence) and transcriptomic (RNA-sequence) data for testing whether increased BMI alters the subnuclear compartmentalization of open chromatin in the twins' preadipocytes, causing downstream inflammation. Here we show that the co-accessibility of open chromatin, i.e. compartmentalization of chromatin activity, is altered in the higher vs lower BMI MZ siblings for a large subset ( ~ 88.5 Mb) of the active subnuclear compartments. Using the UK Biobank we show that variants within these regions contribute to systemic inflammation through interactions with BMI on C-reactive protein. In summary, open chromatin co-accessibility in human preadipocytes is disrupted among the higher BMI siblings, suggesting a mechanism how obesity may lead to inflammation via gene-environment interactions.</p>
14 Authors
- Kristina M. Garske
- Asha Kar
- Caroline Comenho
- Brunilda Balliu
- David Z. Pan
- Yash V. Bhagat
- Gregory Rosenberg
- Amogha Koka
- Sankha Subhra Das
- Zong Miao
- Janet S. Sinsheimer
- Jaakko Kaprio
- Kirsi H. Pietiläinen
- Päivi Pajukanta
1 Application
| Application ID | Title |
|---|---|
| 33934 | Identification of gene-environment interactions and causal pathways for obesogenic cardiometabolic diseases |
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