AI Article Synopsis
- Obesity can lead to inflammation and related health issues due to dysfunction in fat tissue.
- In this study, researchers examined preadipocytes (fat cells) from identical twins with different BMIs to understand how increased BMI affects chromatin structure and its role in inflammation.
- Findings reveal that higher BMI alters the accessibility of chromatin in these cells, which is linked to higher levels of systemic inflammation, suggesting a genetic and environmental interaction that contributes to obesity-related issues.
Article 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.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10349101 | PMC |
| http://dx.doi.org/10.1038/s41467-023-39919-y | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
, the most common non-viral sexually transmitted parasite, causes more than 270 million infections annually. The infection's outcome varies greatly depending on different factors that include variation in human immune responses, the vaginal microbiome, and the inherent virulence of the strain. Although the pathogenicity of the different strains depends, at least partially, on differential gene expression of virulence genes; the regulatory mechanisms governing this transcriptional control remain incompletely understood.
View Article and Find Full Text PDFStarvation, intermittent fasting and exercise, all of which are recommended lifestyle modifiers share a common metabolic signature, ketogenesis to generate the ketone bodies, predominantly β-hydroxybutyrate. β-hydroxybutyrate exerts beneficial effects across various contexts, preventing or mitigating disease. We hypothesized that these dynamic health benefits of β-hydroxybutyrate might stem from its ability to regulate genome architecture through chromatin remodeling via histone β-hydroxybutyrylation, thereby influencing the transcriptome.
View Article and Find Full Text PDFUnlabelled: In most cancers, including endometrial cancer, tumor suppressor genes harboring inactivating mutations have been systematically cataloged. However, locus-specific epigenetic alterations contributing to cancer initiation and progression remain only partly described, creating knowledge gaps about functionally significant tumor suppressors and underlying mechanisms associated with their inactivation. Here, we show that PAX2 is an endometrial tumor suppressor recurrently inactivated by a distinct epigenetic reprogramming event not associated with promoter hypermethylation.
View Article and Find Full Text PDFAn evaluation framework for clinical use of large language models in patient interaction tasks.
Nat Med
January 2025
Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
The integration of large language models (LLMs) into clinical diagnostics has the potential to transform doctor-patient interactions. However, the readiness of these models for real-world clinical application remains inadequately tested. This paper introduces the Conversational Reasoning Assessment Framework for Testing in Medicine (CRAFT-MD) approach for evaluating clinical LLMs.
View Article and Find Full Text PDFLong non-coding RNAs direct the SWI/SNF complex to cell type-specific enhancers.
Nat Commun
January 2025
Goethe University Frankfurt, Institute for Cardiovascular Physiology, Frankfurt, Germany.
The coordination of chromatin remodeling is essential for DNA accessibility and gene expression control. The highly conserved and ubiquitously expressed SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex plays a central role in cell type- and context-dependent gene expression. Despite the absence of a defined DNA recognition motif, SWI/SNF binds lineage specific enhancers genome-wide where it actively maintains open chromatin state.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!