Aregs-IGFBP3-mediated SMC-like cells apoptosis impairs beige adipocytes formation in aged mice.
Level 5 - mechanism / opinion, no new human data
Preclinical animal and in vitro cell culture study with no human data.
PubMed 40118146 · doi:10.1016/j.molmet.2025.102125
What was done
The authors examined the role of adipose stem and progenitor cells, specifically the CD142+ adipogenesis-regulatory cells (Aregs) subpopulation, in beige adipocyte formation in aged mice under cold stimulation. They evaluated Areg dynamics in subcutaneous white adipose tissue (sWAT), performed functional enrichment and signaling pathway analysis on smooth muscle cell-like (SMC-like) cells, evaluated molecular interactions with IGFBP3 (including Egfr, Irf1, and Cdkn1a), and conducted in vitro co-culture assays to measure the impact of IGFBP3 on beige adipogenesis.
What was found
The abstract reports directional findings without numerical values. Cold exposure significantly increased Aregs in the sWAT of aged mice. Aregs secreted IGFBP3, which promoted apoptosis and fibrotic pathways in SMC-like cells via activation of TGFβ, MAPK, and p53 signaling and interaction with Egfr, Irf1, and Cdkn1a. In co-culture assays, IGFBP3 significantly suppressed beige adipocyte formation.
Why it matters
This study defines a cellular and molecular mechanism—Areg-derived IGFBP3 inducing apoptosis in SMC-like progenitor cells—that contributes to the loss of white adipose tissue browning during aging. These pathways present potential preclinical targets for addressing age-associated metabolic dysfunction.
Limits
Findings are limited to aged mouse models and in vitro co-culture assays; translatability to human adipose tissue biology is unproven. The abstract provides no specific sample sizes, effect sizes, or statistical metrics. In vivo rescue interventions targeting IGFBP3 are not specified in the abstract.
Cited by
- supports In mice, the ability to generate new brown fat or convert white fat to beige fat declines with advancing age.