Journal
NATURE COMMUNICATIONS
Volume 14, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-023-39919-y
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Obesity-induced adipose tissue dysfunction can lead to chronic low-grade inflammation and other comorbidities. This study used human primary preadipocytes from monozygotic twins with different body mass index (BMI) to investigate the impact of increased BMI on subnuclear chromatin compartmentalization and downstream inflammation. The results showed that open chromatin co-accessibility was altered in higher BMI twins compared to lower BMI twins, suggesting a mechanism through which obesity may induce inflammation through gene-environment interactions. Furthermore, variants within these regions were found to contribute to systemic inflammation in association with BMI and C-reactive protein levels.
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 (similar to 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.
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