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The Role of O-GlcNAc Transferase in Brown Adipose Tissue Metabolism and Energy Homeostasis
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The Role of O-GlcNAc Transferase in Brown Adipose Tissue Metabolism and Energy Homeostasis
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Dissertation
The Role of O-GlcNAc Transferase in Brown Adipose Tissue Metabolism and Energy Homeostasis
2018
Overview
Brown adipose tissue (BAT) is a key thermogenic tissue that is also important for systemic metabolism. BAT forms during embryonic development, yet master regulators required for the maintenance of adult BAT identity and function remain obscure. O-linked β-D-N-acetylglucosamine modification (O-G1cNAcylation) is a nutrient-sensing post-translational modification that targets many intracellular proteins and regulates a myriad of cellular processes. Here we report that inducible deletion of O-GlcNAc transferase (OGT) in adult BAT triggers whitening of BAT. OGT-deficient BAT shows tissue hypertrophy, increased triglyceride deposition, and enlarged lipid droplets. Transcriptomic analysis of OGT-ablated BAT reveals that expression levels of thermogenic genes are unchanged, whereas expression of genes involved in anabolic programs are upregulated. Mass Isotopomeric Multiordinate Spectral Analysis (MIMOSA) shows enhanced TCA cycle cataplerosis contributing to lipid synthesis. Collectively, our findings reveal that OGT is vital for governing the genetic and metabolic identities of BAT, thereby preventing the whitening of adult BAT and systemic metabolic dysfunction.
Publisher
ProQuest Dissertations & Theses
Subject
ISBN
9780438269637, 0438269632
