Adipocyte · Published 2026-07-03 · DOI 10.1080/21623945.2026.2682671
Kazuki Maekawa, Fumika Yokoyama, Rie Tsutsumi, Akiko Tateishi, Akifumi Maeda, Norifumi Tateishi
β-Adrenergic receptors (β-ARs) drive the induction of beige adipocytes in rodents and humans, yet the dominant human subtype, β2-AR or β3-AR, remains debated. This study aimed to confirm whether human adipose-derived mesenchymal stem cell (hADSCs)-derived adipocytes can serve as a beiging-competent model under human-relevant browning stimuli and to compare the involvement of β2-AR and β3-AR in hADSCs-derived beige adipocyte differentiation. hADSCs were differentiated into adipocytes using an adipogenic cocktail in the presence or absence of human-relevant browning stimuli or β2-AR/β3-AR-selective agonists with or without β2-AR/β3-AR-selective antagonists. Non-selective β-AR activation induces beige adipogenesis along with mRNA and/or protein expression of beiging markers, including uncoupling protein 1 (UCP1), appearance of multilocular adipocytes, and enhanced mitochondrial respiratory readouts. Moreover, norepinephrine, forskolin, and trigonelline increased mRNA and/or protein expression of UCP1. Pharmacological dissection with subtype-selective agonists and antagonists revealed that activation of β2-AR, but not β3-AR, is necessary and sufficient for inducing UCP1. The β2-AR blockade abolished UCP1 upregulation, whereas the β3-AR blockade had minimal effects. β2-selective stimulation recapitulated the beiging response. This study establishes hADSCs-derived adipocytes as a practicable, human-relevant platform for screening pharmacological agents and food-derived compounds and identifies β2-AR as a translationally actionable target for inducing beige adipocytes in humans.
Abstract from DOAJ. Public domain (CC0 1.0).
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Maekawa, K., Yokoyama, F., Tsutsumi, R., et al. (2026). β2-adrenergic receptor stimulation drives differentiation of human adipose-derived mesenchymal stem cells into beige adipocytes. Adipocyte. https://doi.org/10.1080/21623945.2026.2682671