Distinct adipose progenitor cells emerging with age drive active adipogenesis.

Summary

This study identifies an age-enriched committed preadipocyte (CP-A) population that drives mid-life visceral adipogenesis. CP-A expansion and adipogenic activity require leukemia inhibitory factor receptor (LIFR) signaling, highlighting a targetable mechanism for age-dependent adipose remodeling.

Key Findings

• Lineage tracing shows extensive visceral adipogenesis during middle age despite low turnover in youth.
• Single-cell RNA-seq identifies an age-enriched committed preadipocyte (CP-A) population with heightened proliferation and adipogenesis.
• LIFR signaling is indispensable for CP-A-driven adipogenesis and visceral fat expansion; perturbation of LIFR impairs these processes.
• Transplantation demonstrates middle-aged APCs have higher cell-autonomous adipogenic capacity.

Clinical Implications

Targeting LIFR signaling or CP-A biology could offer new strategies to prevent or reverse age-related visceral adiposity and downstream metabolic disorders.

Limitations

• Mouse-based preclinical findings; human validation of CP-A and LIFR dependence remains to be established.
• Depot- and sex-specific effects and long-term safety of targeting LIFR are not addressed.

Future Directions

Validate CP-A and LIFR signaling in human adipose depots across ages; assess therapeutic modulation of LIFR/ligands in obesity and metabolic disease models.