IFG2 Drives Proliferation of Fat Precursor Cells
Adipose tissue is not merely an energy storage depot; it comprises specialized precursor cells that undergo proliferation and differentiation, particularly during early postnatal development. Researchers identified a distinct population of DPP4-positive preadipocytes in mouse subcutaneous fat that express IGF2. Instead of undergoing immediate differentiation into mature adipocytes, these cells respond to IGF2 signaling by proliferating, thereby expanding the preadipocyte pool and supporting the proper growth and development of adipose tissue.
Loss of IGF2 Accelerates Adipocyte Differentiation
When IGF2 is ablated in these precursor cells, they undergo premature differentiation into mature adipocytes. These findings indicate that IGF2 functions as a regulator of preadipocyte proliferation, maintaining the cells in a proliferative and undifferentiated state during early postnatal development. Proper temporal regulation of IGF2 signaling may be critical for preventing dysregulated adipose tissue expansion and associated metabolic complications later in life.
Implications for Obesity and Metabolic Health
“This study provides mechanistic insight into early-life adipose tissue development and highlights the importance of temporal regulation for metabolic homeostasis,” so Siegfried Ussar, senior author of the study. “By elucidating how IGF2 governs the expansion of fat precursor cells, we gain a better understanding of the biological factors that influence susceptibility to obesity and metabolic disorders, potentially informing strategies to promote healthier adipose tissue development.”
The research team anticipates that these findings will inform further investigations into metabolically healthy obesity, the impact of early-life nutrition on adipose tissue development, and potential interventions aimed at optimizing long-term metabolic health.
Original Publication
Altun et al., 2025: Igf2 regulates early postnatal DPP4+ preadipocyte pool expansion. Genes & Development. DOI: 10.1101/gad.352710.125
