1499-P: Adipocyte Development from Mesenchymal Progenitor Cells Differ between Subjects with Normal Glucose Tolerance or Type 2 Diabetes
Subcutaneous adipose tissue protects from T2D by sequestering lipids and preventing lipotoxicity and insulin resistance. Adipose depots are maintained throughout the lifetime by the formation of new adipocytes from mesenchymal progenitor cells that reside within the tissue. In previous studies, we h...
Gespeichert in:
Veröffentlicht in: | Diabetes (New York, N.Y.) N.Y.), 2023-06, Vol.72 (Supplement_1), p.1 |
---|---|
Hauptverfasser: | , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
Zusammenfassung: | Subcutaneous adipose tissue protects from T2D by sequestering lipids and preventing lipotoxicity and insulin resistance. Adipose depots are maintained throughout the lifetime by the formation of new adipocytes from mesenchymal progenitor cells that reside within the tissue. In previous studies, we have found that mesenchymal progenitor cells from human adipose tissue can be expanded with little loss of multipotency by culturing tissue explants in 3-dimensional hydrogels under pro-angiogenic conditions. Mesenchymal progenitor cells obtained in this manner can be induced to differentiate into multiple adipocyte subtypes, including beige adipocytes characterized by their induction of UCP1 upon cAMP elevation. Using this approach, we explored whether mesenchymal progenitor cells from the subcutaneous abdominal (ABD) and gluteal (GLU) depots of subjects with normal glucose tolerance (NGT) or T2D would differ in their capacity to differentiate into adipocyte subtypes. Results from n=12 subjects (6 with NGT and 6 with T2D) revealed no significant differences between depots or glycemic states in the number of mesenchymal progenitor cells that can be expanded, in their proliferative rate upon subsequent passaging, or in their capacity to differentiate into either white or beige adipocytes. However, we found that cells from either the ABD or GLUT depot from NGT subjects displayed substantial spontaneous adipocyte differentiation even without adipogenic induction, but cells from subjects with T2D did not. This difference was highly significant, and potentially reflects a diminished capacity of mesenchymal progenitor cells to maintain subcutaneous adipose depots in-vivo in subjects with T2D. Further transcriptomic and epigenomic analyses of expanded progenitor cells, currently underway, has the potential to reveal cellular mechanisms of impaired spontaneous adipocyte differentiation in subjects with Type 2 Diabetes. |
---|---|
ISSN: | 0012-1797 1939-327X |
DOI: | 10.2337/db23-1499-P |