Adipocyte Piezo1 mediates obesogenic adipogenesis through the FGF1/FGFR1 signaling pathway in mice

ShengPeng Wang (), Shuang Cao, Malika Arhatte, Dahui Li, Yue Shi, Sabrina Kurz, Jiong Hu, Lei Wang, Jingchen Shao, Ann Atzberger, Zheng Wang, Changhe Wang, Weijin Zang, Ingrid Fleming, Nina Wettschureck, Eric Honoré and Stefan Offermanns ()
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ShengPeng Wang: Max Planck Institute for Heart and Lung Research, Department of Pharmacology
Shuang Cao: Max Planck Institute for Heart and Lung Research, Department of Pharmacology
Malika Arhatte: Université Côte d’Azur, Centre National de la Recherche Scientifique, Institut de Pharmacologie Moléculaire et Cellulaire, Labex ICST
Dahui Li: The University of Hong Kong
Yue Shi: Xi’an Jiaotong University Health Science Center, Key Laboratory of Environment and Genes Related to Diseases
Sabrina Kurz: Max Planck Institute for Heart and Lung Research, Department of Pharmacology
Jiong Hu: Goethe University
Lei Wang: Max Planck Institute for Heart and Lung Research, Department of Pharmacology
Jingchen Shao: Max Planck Institute for Heart and Lung Research, Department of Pharmacology
Ann Atzberger: Flow Cytometry Service Group
Zheng Wang: First Affiliated Hospital of Xi’an Jiaotong University
Changhe Wang: Xi’an Jiaotong University
Weijin Zang: Xi’an Jiaotong University Health Science Center
Ingrid Fleming: Goethe University
Nina Wettschureck: Max Planck Institute for Heart and Lung Research, Department of Pharmacology
Eric Honoré: Université Côte d’Azur, Centre National de la Recherche Scientifique, Institut de Pharmacologie Moléculaire et Cellulaire, Labex ICST
Stefan Offermanns: Max Planck Institute for Heart and Lung Research, Department of Pharmacology

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: Abstract White adipose tissue (WAT) expansion in obesity occurs through enlargement of preexisting adipocytes (hypertrophy) and through formation of new adipocytes (adipogenesis). Adipogenesis results in WAT hyperplasia, smaller adipocytes and a metabolically more favourable form of obesity. How obesogenic WAT hyperplasia is induced remains, however, poorly understood. Here, we show that the mechanosensitive cationic channel Piezo1 mediates diet-induced adipogenesis. Mice lacking Piezo1 in mature adipocytes demonstrated defective differentiation of preadipocyte into mature adipocytes when fed a high fat diet (HFD) resulting in larger adipocytes, increased WAT inflammation and reduced insulin sensitivity. Opening of Piezo1 in mature adipocytes causes the release of the adipogenic fibroblast growth factor 1 (FGF1), which induces adipocyte precursor differentiation through activation of the FGF-receptor-1. These data identify a central feed-back mechanism by which mature adipocytes control adipogenesis during the development of obesity and suggest Piezo1-mediated adipocyte mechano-signalling as a mechanism to modulate obesity and its metabolic consequences.

Date: 2020
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DOI: 10.1038/s41467-020-16026-w

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