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

Byung Chul Jung; Dongjoo You; Ikjun Lee; Daofeng Li; Rebecca L. Schill; Katherine Ma; Anna Pi; Zehan Song; Wei-Chieh Mu; Ting Wang; Ormond A. MacDougald; Alexander S. Banks; Sona Kang

Cell Reports (Oct 2023)

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

Byung Chul Jung,
Dongjoo You,
Ikjun Lee,
Daofeng Li,
Rebecca L. Schill,
Katherine Ma,
Anna Pi,
Zehan Song,
Wei-Chieh Mu,
Ting Wang,
Ormond A. MacDougald,
Alexander S. Banks,
Sona Kang

Affiliations

Byung Chul Jung: Nutritional Sciences and Toxicology Department, University of California Berkeley, Berkeley, CA, USA
Dongjoo You: Nutritional Sciences and Toxicology Department, University of California Berkeley, Berkeley, CA, USA
Ikjun Lee: Nutritional Sciences and Toxicology Department, University of California Berkeley, Berkeley, CA, USA
Daofeng Li: Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA; The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA
Rebecca L. Schill: Department of Molecular & Integrative Physiology, University of Michigan School of Medicine, Ann Arbor, MO, USA
Katherine Ma: Nutritional Sciences and Toxicology Department, University of California Berkeley, Berkeley, CA, USA
Anna Pi: Nutritional Sciences and Toxicology Department, University of California Berkeley, Berkeley, CA, USA
Zehan Song: Nutritional Sciences and Toxicology Department, University of California Berkeley, Berkeley, CA, USA
Wei-Chieh Mu: Nutritional Sciences and Toxicology Department, University of California Berkeley, Berkeley, CA, USA
Ting Wang: Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA; The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA
Ormond A. MacDougald: Department of Molecular & Integrative Physiology, University of Michigan School of Medicine, Ann Arbor, MO, USA
Alexander S. Banks: Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
Sona Kang: Nutritional Sciences and Toxicology Department, University of California Berkeley, Berkeley, CA, USA; Corresponding author

Journal volume & issue: Vol. 42, no. 10
p. 113196

Abstract

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Summary: Maintaining healthy adipose tissue is crucial for metabolic health, requiring a deeper understanding of adipocyte 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 adipogenesis and remodeling. DNA methylation profiling and functional studies underscore the importance of DNA demethylation 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.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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