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Anti-adipogenic signals at the onset of obesity-related inflammation in white adipose tissue.

Authors
  • Caputo, Tiziana1
  • Tran, Van Du T2
  • Bararpour, Nasim3, 4
  • Winkler, Carine1
  • Aguileta, Gabriela1
  • Trang, Khanh Bao1
  • Giordano Attianese, Greta M P1
  • Wilson, Anne5
  • Thomas, Aurelien3, 4
  • Pagni, Marco2
  • Guex, Nicolas2, 6
  • Desvergne, Béatrice7
  • Gilardi, Federica8, 9, 10
  • 1 Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland. , (Switzerland)
  • 2 Vital-IT Group, SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland. , (Switzerland)
  • 3 Unit of Forensic Toxicology and Chemistry, CURML, Lausanne University Hospital, Geneva University Hospitals, Lausanne, Switzerland. , (Switzerland)
  • 4 Faculty Unit of Toxicology, Faculty of Biology and Medicine, CURML, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland. , (Switzerland)
  • 5 Department of Oncology, University of Lausanne, Epalinges, Switzerland. , (Switzerland)
  • 6 Bioinformatics Competence Center, University of Lausanne, Lausanne, Switzerland. , (Switzerland)
  • 7 Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland. [email protected]. , (Switzerland)
  • 8 Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland. [email protected]. , (Switzerland)
  • 9 Unit of Forensic Toxicology and Chemistry, CURML, Lausanne University Hospital, Geneva University Hospitals, Lausanne, Switzerland. [email protected]. , (Switzerland)
  • 10 Faculty Unit of Toxicology, Faculty of Biology and Medicine, CURML, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland. [email protected]. , (Switzerland)
Type
Published Article
Journal
Cellular and Molecular Life Sciences
Publisher
Springer-Verlag
Publication Date
Jan 01, 2021
Volume
78
Issue
1
Pages
227–247
Identifiers
DOI: 10.1007/s00018-020-03485-z
PMID: 32157317
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Chronic inflammation that affects primarily metabolic organs, such as white adipose tissue (WAT), is considered as a major cause of human obesity-associated co-morbidities. However, the molecular mechanisms initiating this inflammation in WAT are poorly understood. By combining transcriptomics, ChIP-seq and modeling approaches, we studied the global early and late responses to a high-fat diet (HFD) in visceral (vWAT) and subcutaneous (scWAT) AT, the first being more prone to obesity-induced inflammation. HFD rapidly triggers proliferation of adipocyte precursors within vWAT. However, concomitant antiadipogenic signals limit vWAT hyperplastic expansion by interfering with the differentiation of proliferating adipocyte precursors. Conversely, in scWAT, residing beige adipocytes lose their oxidizing properties and allow storage of excessive fatty acids. This phase is followed by tissue hyperplastic growth and increased angiogenic signals, which further enable scWAT expansion without generating inflammation. Our data indicate that scWAT and vWAT differential ability to modulate adipocyte number and differentiation in response to obesogenic stimuli has a crucial impact on the different susceptibility to obesity-related inflammation of these adipose tissue depots.

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