Authors:

Sedje Tinfang

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About Paper:

Beige adipocytes within inguinal white adipose tissue (iWAT)-contribute to thermogenesis and energy expenditure and represent a potential target for obesity-related metabolic disorders [1]. However, the molecular mechanisms regulating beige adipocyte formation remain incompletely understood. We hypothesized that estrogen receptor alpha (ERa) signaling in platelet-derived growth factor receptor alpha—positive (PDGFRa') progenitor cells is required for beige adipogenesis [2]. To test this hypothesis, we generated Pdgfra-specific ERa knockout mice (PRa—-ERa KO) and evaluated beige fat formation under cold exposure. Loss of ERa in PDGFRa* cells resulted in impaired cold-induced beige adipocyte differentiation, reduced thermogenic gene expression, increased adipose tissue fibrosis, and metabolic dysfunction. Mechanistic analyses revealed that ERa deletion enhanced transforming growth factor beta (TGF) signaling, which suppressed the differentiation of smooth muscle actin—positive (SMA*) progenitor cells into beige adipocytes. Pharmacological inhibition of TGFB signaling using the small-molecule inhibitor CJJ300 restored beige adipogenesis in PRa-ERa KO mice, reduced fibrotic remodeling, and improved thermogenic capacity. Notably, aged mice exhibited similar defects in beige fat formation and thermogenic function, which were also substantially rescued by CJJ300 treatment. Together, these findings identify ERa-TGFFf signaling crosstalk in PDGFRo* progenitor cells as a critical regulatory pathway governing beige adipocyte biogenesis. Targeting TGFB signaling may therefore represent a promising therapeutic strategy to enhance thermogenesis and counteract obesity-associated metabolic decline, particularly in aging populations.

Source:

University of Illinois Chicago

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Co-authors:

Sedje Tinfang