Scientists from City of Hope and UCLA identify a novel age-specific adipocyte progenitor cell population (CP-As) that proliferates and differentiates into fat cells in middle-aged mice. Using single-cell RNA sequencing and in vivo lineage tracing, they pinpoint the LIFR signaling pathway as critical for CP-A mediated adipogenesis. Inhibiting LIFR signaling prevents visceral fat expansion, suggesting a promising strategy to mitigate age-related obesity and metabolic dysfunction.

Key points

• Discovery of CP-As: age-specific committed preadipocytes emerge in middle-aged adipose tissue.
• LIFR signaling: critical driver of CP-A proliferation and differentiation into new adipocytes.
• Lineage tracing & 3D APC transplants confirm autonomous fat-generating capacity of aged APCs.
• Single-cell RNA sequencing delineates gene expression profiles distinguishing CP-As from other APCs.
• Pharmacological LIFR inhibition prevents visceral fat expansion without affecting young APC adipogenesis.

Why it matters: By uncovering CP-As and their LIFR-driven adipogenesis, this work shifts the paradigm of age-related fat expansion, highlighting adipogenesis rather than hypertrophy as a major contributor. Targeting LIFR offers a precise therapeutic avenue to curb visceral obesity and metabolic disorders in middle-aged populations.