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Age-dependent Pdgfrβ signaling drives adipocyte progenitor dysfunction to alter the beige adipogenic niche in male mice
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Age-dependent Pdgfrβ signaling drives adipocyte progenitor dysfunction to alter the beige adipogenic niche in male mice
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Age-dependent Pdgfrβ signaling drives adipocyte progenitor dysfunction to alter the beige adipogenic niche in male mice
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Journal Article
Age-dependent Pdgfrβ signaling drives adipocyte progenitor dysfunction to alter the beige adipogenic niche in male mice
2023
Overview
Perivascular adipocyte progenitor cells (APCs) can generate cold temperature-induced thermogenic beige adipocytes within white adipose tissue (WAT), an effect that could counteract excess fat mass and metabolic pathologies. Yet, the ability to generate beige adipocytes declines with age, creating a key challenge for their therapeutic potential. Here we show that ageing beige APCs overexpress platelet derived growth factor receptor beta (
Pdgfrβ
) to prevent beige adipogenesis. We show that genetically deleting
Pdgfrβ
, in adult male mice, restores beige adipocyte generation whereas activating
Pdgfrβ
in juvenile mice blocks beige fat formation. Mechanistically, we find that Stat1 phosphorylation mediates Pdgfrβ beige APC signaling to suppress
IL-33
induction, which dampens immunological genes such as
IL-13
and
IL-5
. Moreover, pharmacologically targeting Pdgfrβ signaling restores beige adipocyte development by rejuvenating the immunological niche. Thus, targeting Pdgfrβ signaling could be a strategy to restore WAT immune cell function to stimulate beige fat in adult mammals.
Thermogenic beige fat can reduce fat mass and improve metabolic health, yet the ability to form beige fat rapidly declines with age. Here, the authors show that targeting the age-related ramping of Pdgfrβ signalling restores the ageing adipose tissue niche to ignite beige fat development.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/100
/ 13/106
/ 13/31
/ 13/51
/ 14/63
/ 38/39
/ 38/91
/ 64
/ 64/60
/ Adipose Tissue, White - metabolism
/ Age
/ Aging
/ Animals
/ Body fat
/ Humanities and Social Sciences
/ Male
/ Males
/ Mice
/ Platelet-derived growth factor
/ Platelet-derived growth factor receptors
/ Receptor, Platelet-Derived Growth Factor beta - genetics
/ Receptor, Platelet-Derived Growth Factor beta - metabolism
/ Science
