ORCID
https://orcid.org/0000-0002-6938-3789
Date of Award
10-19-2023
Degree Name
Doctor of Philosophy (PhD)
Degree Type
Dissertation
Abstract
The adipose tissue is composed of specialized energy storage cells called adipocytes. In white adipose tissue, when committed precursor cells (preadipocytes), receive specific cues, the preadipocytes differentiate into mature adipocytes via an adipogenic gene program promoted by transcription factors such as PPAR. Phosphatidylserine (PS) is a phospholipid asymmetrically maintained on the inner leaflet of the plasma membrane in healthy cells. PS flipping to the outer leaflet is a well-known hallmark of cell death, such as apoptosis. Here, while exploring the interplay between PS exposure and adipose tissue homeostasis, we made a surprising discovery in that non apoptotic PS exposure occurs on a subset of live early adipocytes during adipocyte differentiation, and that masking this PS exposure on differentiating adipocytes blocks adipogenesis. Mechanistically, the scramblase TMEM16F mediates the PS exposure, which is sensed in part via the PS receptor AXL; the subsequent downstream signaling events promote the PPAR dependent transcriptional program toward adipogenesis. Interfering with PS exposure or sensing in vivo impairs fat accumulation in a mouse model. Collectively, these data provide previously unappreciated insights into adipogenesis with implications for obesity.
Language
English (en)
Chair and Committee
Kodi Ravichandran
Recommended Citation
Barron, Brady Jeffrey, "A Thesis on Phosphatidylserine as a Key Signaling Moiety During Adipocyte Differentiation" (2023). Arts & Sciences Electronic Theses and Dissertations. 3180.
https://openscholarship.wustl.edu/art_sci_etds/3180