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ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #426929
Research Project: Regulatory Aspects of Nutritional Metabolism

Location: Children's Nutrition Research Center

Title: Distinct adipose progenitor cells emerging with age drive active adipogenesis

Author
item WANG, GUAN - City Of Hope Medical Center
item LI, GAOYAN - University Of California (UCLA)
item SONG, ANYING - City Of Hope Medical Center
item ZHAO, YUTIAN - University Of California (UCLA)
item YU, JIAYU - City Of Hope Medical Center
item WANG, YIFAN - City Of Hope Medical Center
item DAI, WENTING - City Of Hope Medical Center
item SALAS, MARTHA - City Of Hope Medical Center
item QIN, HANJUN - City Of Hope Medical Center
item MEDRANO, LEONARD - City Of Hope Medical Center
item DOW, JOAN - City Of Hope Medical Center
item LI, AIMIN - City Of Hope Medical Center
item ARMSTRONG, BRIAN - City Of Hope Medical Center
item FUEGER, PATRICK - City Of Hope Medical Center
item YU, HUA - City Of Hope Medical Center
item ZHU, YI - Children'S Nutrition Research Center (CNRC)
item SHAO, MENGLE - Chinese Academy Of Sciences
item WU, XIWEI - City Of Hope Medical Center
item JIANG, LEI - City Of Hope Medical Center
item CAMPISI, JUDITH - Buck Institute For Age Research
item YANG, XIA - University Of California (UCLA)
item WANG, QIONG - City Of Hope Medical Center

Submitted to: Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/25/2025
Publication Date: 4/25/2025
Citation: Wang, G., Li, G., Song, A., Zhao, Y., Yu, J., Wang, Y., Dai, W., Salas, M., Qin, H., Medrano, L., Dow, J., Li, A., Armstrong, B., Fueger, P.T., Yu, H., Zhu, Y., Shao, M., Wu, X., Jiang, L., Campisi, J., Yang, X., Wang, Q.A. 2025. Distinct adipose progenitor cells emerging with age drive active adipogenesis. Science. 388. Article eadj0430. https://doi.org/10.1126/science.adj0430.
DOI: https://doi.org/10.1126/science.adj0430

Interpretive Summary: Scientists discovered that middle-aged male mice (but not females) grow more belly fat because their fat cells multiply rapidly during aging, unlike in younger mice. They found special "super-charged" fat-making cells that appear only in middle age and depend on a protein called LIFR to work. Blocking LIFR stopped belly fat growth, suggesting a new way to fight age-related weight gain and diabetes.

Technical Abstract: 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.