[F32] Effects of exercise training on subcutaneous adipose tissue cellular heterogeneity in adults with obesity
Ente: National Institute of Diabetes and Digestive and Kidney Diseases
Scadenza: 2029-03-31
Importo max: 74.632 EUR
Paese: US
Descrizione
PROJECT SUMMARY
Obesity is associated with impaired lipid storage in abdominal subcutaneous adipose tissue (ASAT), leading to
excessive fatty acid release, ectopic fat accumulation, and insulin resistance. Identifying mechanisms that
contribute to impaired lipid storage and developing strategies to enhance ASAT function are critical for
improving metabolic health in individuals with obesity. While endurance training has been shown to induce
beneficial adaptations in adipose tissue and improve lipid storage capacity, the cellular and molecular
mechanisms remain unclear. My preliminary findings from single-nucleus RNA sequencing (snRNAseq) have
identified a unique adipocyte subtype, Adipocyte-2, enriched with insulin-responsive and lipogenic genes and
associated with improved metabolic health markers, including lower ectopic fat and higher endothelial cell
abundance. Additionally, my ex vivo data demonstrate adipocyte heterogeneity in insulin-stimulated lipid
uptake, suggesting that Adipocyte-2 may be a metabolically favorable subtype with enhanced lipid storage
capacity. Building upon these findings, this project will determine whether a 3-month endurance training
intervention, independent of weight loss, improves Adipocyte-2 abundance, transcriptional profile, and spatial
localization, contributing to improved lipid storage and cardiometabolic health in adults with obesity. Aim 1 will
assess the relationship of Adipocyte-2 abundance, transcriptional profile, and spatial localization with insulin
sensitivity, along with its ex vivo lipid uptake capacity, using ASAT microdialysis during a hyperinsulinemic
clamp and functional adipocyte assays. Aim 2 will investigate whether 3 months of endurance training
increases Adipocyte-2 abundance and transcriptional profile and alters its spatial positioning within ASAT,
specifically in relation to endothelial cells, pericytes, and macrophages, and how these adaptations contribute
to improved cardiometabolic health. By integrating clinical exercise interventions with advanced molecular
techniques, including snRNAseq, spatial transcriptomics, and functional assays, this project will define the role
of adipocyte heterogeneity in exercise-induced metabolic adaptations. Under the mentorship of Dr. Lauren
Sparks, an expert in human translational metabolism, and a collaborative team of specialists in metabolism
and bioinformatics, this training plan will provide me with the skills and expertise necessary to establish an
independent research career focused on exercise, adipose tissue function, and cardiometabolic health.
Istituzione: ADVENTHEALTH ORLANDO
PI: Cheehoon Ahn
Progetto: 1F32DK146553-01
Settori: National Institute of Diabetes and Digestive and Kidney Diseases
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