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Rapid depot-specific activation of adipocyte precursor cells at the onset of obesity
Open accessAbstract
Excessive accumulation of white adipose tissue (WAT) is the defining characteristic of obesity. WAT mass is composed primarily of mature adipocytes, which are generated through the proliferation and differentiation of adipocyte precursors (APs). Although the production of new adipocytes contributes to WAT growth in obesity, little is known about the cellular and molecular mechanisms underlying adipogenesis in vivo. Here, we show that high-fat diet feeding in mice rapidly and transiently induces proliferation of APs within WAT to produce new adipocytes. Importantly, the activation of adipogenesis is specific to the perigonadal visceral depot in male mice, consistent with the patterns of obesogenic WAT growth observed in humans. Furthermore, we find that in multiple models of obesity, the activation of APs is dependent on the phosphoinositide 3-kinase (PI3K)-AKT2 pathway; however, the development of WAT does not require AKT2. These data indicate that developmental and obesogenic adipogenesis are regulated through distinct molecular mechanisms.
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“Male mice develop diet-induced obesity primarily though visceral fat hyperplasia, while female mice do so via both visceral and subcutaneous fat hyperplasia (70, 71) with sex steroids playing a major role (70, 72).”
From Metabolic impact of endogenously produced estrogens by adipose tissue in females and males across the lifespan (2025) · cites this paper as [71]
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Metadata
- Authors
- Jeffery, E., Church, C. D., Holtrup, B., Colman, L., & Rodeheffer, M. S.
- Affiliations
- Yale University (US)
- Corresponding author
- Rodeheffer, Matthew S.
- Venue
- Nature Cell Biology
- Published
- 2015-03-02
- Volume
- 17
- Issue
- 4
- Pages
- 376-385
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- PMC
- PMC4380653
- OpenAlex
- W2000524154
- Cited by
- 404
- References
- 53
- Citations by year
- 2026: 14 · 2025: 26 · 2024: 29 · 2023: 44 · 2022: 42 · 2021: 39 · 2020: 39 · 2019: 42 · 2018: 37 · 2017: 40 · 2016: 35 · 2015: 16
- FWCI
- 33.45
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (UL1TR000142)
- National Institute of General Medical Sciences (T32GM007223)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK090489, R56DK090489, DK-045735, DK090489, P30DK045735)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- adipocyte precursors, adipogenesis, obesity, white adipose tissue, high-fat diet, adipocyte proliferation
- MeSH terms
- Wortmannin, Phosphoinositide-3 Kinase Inhibitors, Androstadienes, Animals, Eating, Male, Mice, Inbred C57BL, Obesity, Random Allocation, Tamoxifen, Mice, Knockout, Phosphatidylinositol 3-Kinases, Cell Proliferation, Adipogenesis, Proto-Oncogene Proteins c-akt, Mice, Adipose Tissue, White, Adipocytes, White, Diet, High-Fat
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