Children’s Nutrition Research Center Staff Publications

Language

English

Publication Date

4-25-2025

Journal

Science

DOI

10.1126/science.adj0430

PMID

40273250

PMCID

PMC12445215

PubMedCentral® Posted Date

10-25-2025

PubMedCentral® Full Text Version

Author MSS

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.

Keywords

Animals, Male, Mice, Adipocytes, Adipogenesis, Aging, Cell Proliferation, Intra-Abdominal Fat, Mice, Inbred C57BL, Signal Transduction, Single-Cell Analysis, Stem Cells, Female

Published Open-Access

yes

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