1. Increased body mass index is linked to systemic inflammation through altered chromatin co-accessibility in human preadipocytes.
- Author
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Garske, Kristina M., Kar, Asha, Comenho, Caroline, Balliu, Brunilda, Pan, David Z., Bhagat, Yash V., Rosenberg, Gregory, Koka, Amogha, Das, Sankha Subhra, Miao, Zong, Sinsheimer, Janet S., Kaprio, Jaakko, Pietiläinen, Kirsi H., and Pajukanta, Päivi
- Subjects
HUMAN chromatin ,BODY mass index ,TWINS ,GENOTYPE-environment interaction ,INFLAMMATION ,C-reactive protein ,CHROMATIN - 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. Preadipocytes contribute to the pro-inflammatory environment in obesity, via unknown mechanisms. Here, comparing monozygotic twin pairs, the authors show that co-accessibility of chromatin in preadipocytes is altered in siblings with higher compared to lower BMI, and that variants in these regions contribute to systemic inflammation via interactions with BMI. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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