4.8 Article

TET3 plays a critical role in white adipose development and diet-induced remodeling

Journal

CELL REPORTS
Volume 42, Issue 10, Pages -

Publisher

CELL PRESS
DOI: 10.1016/j.celrep.2023.113196

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This study reveals the significant role of TET3 in the development and expansion of white adipose tissue. Depletion of Tet3 reduces adipogenesis, protects against diet-induced adipose expansion, and enhances whole-body metabolism. The study also highlights the importance of DNA demethylation in gene regulation.
Maintaining healthy adipose tissue is crucial for metabolic health, requiring a deeper understanding of adipo-cyte development and response to high-calorie diets. This study highlights the importance of TET3 during white adipose tissue (WAT) development and expansion. Selective depletion of Tet3 in adipose precursor cells (APCs) reduces adipogenesis, protects against diet-induced adipose expansion, and enhances whole-body metabolism. Transcriptomic analysis of wild-type and Tet3 knockout (KO) APCs unveiled TET3 target genes, including Pparg and several genes linked to the extracellular matrix, pivotal for adipogen-esis and remodeling. DNA methylation profiling and functional studies underscore the importance of DNA de-methylation in gene regulation. Remarkably, targeted DNA demethylation at the Pparg promoter restored its transcription. In conclusion, TET3 significantly governs adipogenesis and diet-induced adipose expansion by regulating key target genes in APCs.

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