Publications by authors named "K M Garske"

Given the fast-increasing prevalence of obesity and its comorbidities, it would be critical to improve our understanding of the cell-type level differences between the two key human adipose tissue depots, subcutaneous (SAT) and visceral adipose tissue (VAT), in their depot-specific contributions to cardiometabolic health. We integrated cell-type level RNA- and ATAC-seq data from human SAT and VAT biopsies and cell-lines to comprehensively elucidate transcriptomic, epigenetic, and genetic differences between the two fat depots. We identify cell-type marker genes for tissue specificity and functional enrichment, and show through genome-wide association study (GWAS) and partitioned polygenic risk score (PRS) enrichment analyses that the marker genes upregulated in SAT adipocytes have more prominent roles in abdominal obesity than those of VAT.

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Article Synopsis
  • Abdominal obesity is linked to an increased risk of metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD).
  • The study employed advanced genetic analysis methods, including RNA sequencing and Mendelian randomization, to explore how specific genes related to abdominal obesity impact MASLD at the cellular level.
  • The research identified 17 key genes that mediate the effects of abdominal obesity on MASLD, demonstrating significant changes in adipocyte functions and highlighting the importance of these genes in the disease's development.
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Background: Age and obesity are dominant risk factors for several common cardiometabolic disorders, and both are known to impair adipose tissue function. However, the underlying cellular and genetic factors linking aging and obesity on adipose tissue function have remained elusive. Adipose stem and precursor cells (ASPCs) are an understudied, yet crucial adipose cell type due to their deterministic adipocyte differentiation potential, which impacts the capacity to store fat in a metabolically healthy manner.

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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.
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Gene expression variance has been linked to organismal function and fitness but remains a commonly neglected aspect of molecular research. As a result, we lack a comprehensive understanding of the patterns of transcriptional variance across genes, and how this variance is linked to context-specific gene regulation and gene function. Here, we use 57 large publicly available RNA-seq data sets to investigate the landscape of gene expression variance.

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