Distinct adipose progenitor cells emerging with age drive active adipogenesis
Starting at middle age, adults often suffer from visceral adiposity and associated adverse metabolic disorders. Lineage tracing in mice revealed that adipose progenitor cells (APCs) in visceral fat undergo extensive adipogenesis during middle age. Thus, despite the low turnover rate of adipocytes in young adults, adipogenesis is unlocked during middle age. Transplantations quantitatively showed that APCs in middle-aged mice exhibited high adipogenic capacity cell-autonomously. Single-cell RNA sequencing identified a distinct APC population, the committed preadipocyte, age-enriched (CP-A), emerging at this age. CP-As demonstrated elevated proliferation and adipogenesis activity. Pharmacological and genetic manipulations indicated that leukemia inhibitory factor receptor signaling was indispensable for CP-A adipogenesis and visceral fat expansion. These findings uncover a fundamental mechanism of age-dependent adipose remodeling, offering critical insights into age-related metabolic diseases.
Authors
- Yi Zhu (ORCID: https://orcid.org/0000-0003-1650-1363)
- Judith Campisi (ORCID: https://orcid.org/0000-0001-6858-9462)
- Xiwei Wu (ORCID: https://orcid.org/0000-0002-7071-1671)
- Wenting Dai (ORCID: https://orcid.org/0000-0002-8851-5556)
- Anying Song (ORCID: https://orcid.org/0000-0003-0382-5238)
- Mengle Shao (ORCID: https://orcid.org/0000-0002-5488-9904)
- Hua Yu (ORCID: https://orcid.org/0000-0003-0931-1000)
- Brian Armstrong (ORCID: https://orcid.org/0009-0003-5026-2631)
- Patrick T. Fueger (ORCID: https://orcid.org/0000-0003-0602-6458)
- Leonard Medrano (ORCID: https://orcid.org/0000-0002-0782-5473)
- Joan Dow
- Jiayu Yu (ORCID: https://orcid.org/0000-0002-3648-7979)
- Martha Salas (ORCID: https://orcid.org/0009-0006-0159-5896)
- Gaoyan Li
- Hanjun Qin (ORCID: https://orcid.org/0000-0002-0370-0913)
- Xia Yang (ORCID: https://orcid.org/0000-0002-3971-038X)
- Lijun Wang (ORCID: https://orcid.org/0000-0003-2538-8358)
- Aimin Li (ORCID: https://orcid.org/0000-0003-4387-2397)
- Qiong A Wang (ORCID: https://orcid.org/0000-0003-2224-4287)
- Lei Jiang (ORCID: https://orcid.org/0000-0002-8596-556X)
- Yutian Zhao (ORCID: https://orcid.org/0000-0001-9689-1570)
- Guan Wang (ORCID: https://orcid.org/0000-0003-1822-729X)
Institutions
- QB3 (US)
- City Of Hope National Medical Center (US)
- Buck Institute for Research on Aging (US)
- University of California, Los Angeles (US)
- City of Hope (US)
- Children's Nutrition Research Center at Baylor College of Medicine (US)
- Beckman Research Institute
Publication Details
- Journal
- Science
- Published
- 2025-04-24
- DOI
- https://doi.org/10.1126/science.adj0430
- Citations
- 33
- Primary Topic
- Adipose Tissue and Metabolism
- Type
- article
- Field-Weighted Citation Impact
- 38.42