Publications by authors named "P Seale"
The prevalence of childhood obesity is increasing worldwide, along with the associated common comorbidities of type 2 diabetes and cardiovascular disease in later life. Motivated by evidence for a strong genetic component, our prior genome-wide association study (GWAS) efforts for childhood obesity revealed 19 independent signals for the trait; however, the mechanism of action of these loci remains to be elucidated. To molecularly characterize these childhood obesity loci, we sought to determine the underlying causal variants and the corresponding effector genes within diverse cellular contexts.
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- Adipocyte lipolysis plays a crucial role in regulating overall energy levels and metabolic balance, primarily controlled by specific enzymes and their modifications.
- The study identifies IRF2BP2 as a transcriptional repressor that, when deleted, boosts lipolysis in human adipocytes without altering glucose uptake, while its overexpression has the opposite effect.
- The research further reveals that the deletion of IRF2BP2 in mice leads to increased lipolysis and inflammation in adipose tissue, suggesting potential strategies for targeting lipolysis in metabolic disease treatments.
miRNA and mRNA expression signatures in a HFpEF large animal model.
Am J Physiol Heart Circ Physiol
November 2024
Adipocyte lipolysis controls systemic energy levels and metabolic homeostasis. Lipolysis is regulated by post-translational modifications of key lipolytic enzymes. However, less is known about the transcriptional mechanisms that regulate lipolysis.
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- Genome-wide association studies (GWAS) have identified genetic links to autoimmune disorders but don't pinpoint causal variants or affected cell types; this research enhances understanding using advanced 3D genomic datasets.
- By integrating various genomic techniques, the study maps disease-associated variants to likely regulatory effector genes across 57 human cell types, revealing the complex genetic landscape of autoimmune diseases.
- The investigation identifies both shared and specific genetic pathways, leading to the exploration of squalene synthase as a potential drug target for controlling inflammation in conditions like multiple sclerosis and systemic lupus erythematosus.