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Reduced subcutaneous adipogenesis in human hypertrophic obesity is linked to senescent precursor cells

Author

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  • Birgit Gustafson

    (the Sahlgrenska Academy at the University of Gothenburg)

  • Annika Nerstedt

    (the Sahlgrenska Academy at the University of Gothenburg)

  • Ulf Smith

    (the Sahlgrenska Academy at the University of Gothenburg)

Abstract

Inappropriate expansion of the adipose cells in the subcutaneous adipose tissue (SAT) is a characteristic of hypertrophic obesity and of individuals with genetic predisposition for T2D (first-degree relatives; FDR). It is associated with insulin resistance, a dysfunctional, adipose tissue and reduced adipogenesis. We examined the regulation of adipogenesis in human SAT precursor cells and found ZNF521 to be a critical regulator of early adipogenic commitment and precursor cells leaving the cell cycle. However, neither altered upstream signalling nor lack of SAT progenitor cells could explain the reduced adipogenesis in hypertrophic obesity. Instead, we show that progenitor cells undergoing poor differentiation are characterized by senescence, inability to suppress p53/P16INK4 and secretion of factors reducing adipogenesis in non-senescent cells. We found aging, FDR and established T2D to be associated with increased progenitor cell senescence, reduced adipogenesis and hypertrophic expansion of the SAT adipose cells.

Suggested Citation

  • Birgit Gustafson & Annika Nerstedt & Ulf Smith, 2019. "Reduced subcutaneous adipogenesis in human hypertrophic obesity is linked to senescent precursor cells," Nature Communications, Nature, vol. 10(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10688-x
    DOI: 10.1038/s41467-019-10688-x
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    Cited by:

    1. Aina Lluch & Jessica Latorre & Angela Serena-Maione & Isabel Espadas & Estefanía Caballano-Infantes & José M. Moreno-Navarrete & Núria Oliveras-Cañellas & Wifredo Ricart & María M. Malagón & Alejandro, 2023. "Impaired Plakophilin-2 in obesity breaks cell cycle dynamics to breed adipocyte senescence," Nature Communications, Nature, vol. 14(1), pages 1-21, December.

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