[Recorded Webinar is Available Now!] dkNET Webinar: Defining the Spatiotemporal and Molecular Trajectory of Beige Adipogenesis

*Watch recorded webinar here: https://youtu.be/NhKvdr14nMg

dkNET New Investigator Pilot Program in Bioinformatics Awardee Webinar Series

Join dkNET Webinar on Friday, May 12, 2023, 11 am - 12 pm PDT

Presenter: Nabil Rabhi, PhD. Instructor, Department of Biochemistry, Boston University School of Medicine

Abstract 

   The unique capacity of inguinal white adipose tissue (iWAT) to brown has emerged as a promising therapeutic approach for treating obesity and its adverse complications. Both white and beige adipose arise from a subpopulation of perivascular adipocyte progenitor cells. However, the early signaling events controlling ACP differentiation to beige adipocytes are still unknown.

   To uncover the stromal cells heterogeneity during beige adipogenesis, we performed a single cell RNA-sequencing of iWAT under control conditions, treatment with beta3-adrenergic receptor (ADRB3) agonist, or exposure to cold. ScRNA-seq revealed the landscape of APCs undergoing beige adipogenesis. We identified a distinct subpopulation of APCs expressing SM22 (Smooth Muscle Protein 22-Alpha), that is predicated in silico to give rise to multiple cell types composing adipose depot. Using SM22 lineage tracing mouse model, we found that SM22+ APCs accumulate in response to cold and ?3-adrenergic stimulations but only cold-induced their differentiation to beige adipocytes. Further investigations revealed that beige adipogenesis is a multi-step signaling process involving paracrine communication between mature adipocytes and vascular progenitors. This process involves (1) ADRB3 activation of adipocytes, followed by (2) lipids release by mature adipocytes (3) that induce a metabolic switch and ADRB1 expression in SM22+ APCs. Activation of ADRB1 by catecholamine released under cold exposure promotes primed APCs differentiation to beige adipocytes.Altogether, our data uncovered early steps necessary to promote beige adipogenesis.

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