The adipose tissue microenvironment regulates depot-specific adipogenesis in obesity
Open accessAbstract
The sexually dimorphic distribution of adipose tissue influences the development of obesity-associated pathologies. The accumulation of visceral white adipose tissue (VWAT) that occurs in males is detrimental to metabolic health, while accumulation of subcutaneous adipose tissue (SWAT) seen in females may be protective. Here, we show that adipocyte hyperplasia contributes directly to the differential fat distribution between the sexes. In male mice, high-fat diet (HFD) induces adipogenesis specifically in VWAT, while in females HFD induces adipogenesis in both VWAT and SWAT in a sex hormone-dependent manner. We also show that the activation of adipocyte precursors (APs), which drives adipocyte hyperplasia in obesity, is regulated by the adipose depot microenvironment and not by cell-intrinsic mechanisms. These findings indicate that APs are plastic cells, which respond to both local and systemic signals that influence their differentiation potential independent of depot origin. Therefore, depot-specific AP niches coordinate adipose tissue growth and distribution.
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Male mice develop diet-induced obesity primarily through visceral fat hyperplasia, while female mice do so via both visceral and subcutaneous fat hyperplasia.
“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 [70]
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- Authors
- Jeffery, E., Wing, A., Holtrup, B., Sebo, Z., Kaplan, J. L., Saavedra-Peña, R., Church, C. D., Colman, L., Berry, R., & Rodeheffer, M. S.
- Affiliations
- Yale University (US)
- Corresponding author
- Rodeheffer, Matthew S.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2016-07
- Volume
- 24
- Issue
- 1
- Pages
- 142-150
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC4945385
- OpenAlex
- W2428513306
- Semantic Scholar
- 14d4836b147602658442b978ed95166249fdc6b9
- Cited by
- 352
- References
- 47
- Citations by year
- 2026: 21 · 2025: 36 · 2024: 44 · 2023: 27 · 2022: 36 · 2021: 38 · 2020: 38 · 2019: 36 · 2018: 33 · 2017: 37 · 2016: 6
- FWCI
- 30.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Yale University
- National Institutes of Health (UL1TR001863)
- National Institute of General Medical Sciences (T32GM007223)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK090489, R56DK090489, P30DK045735)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- adipose tissue microenvironment, adipogenesis, obesity, sex differences, visceral white adipose tissue, subcutaneous white adipose tissue, adipocyte hyperplasia, adipocyte precursors, high-fat diet, sex hormones, adipose depots, body fat distribution
- MeSH terms
- Adipose Tissue, Animals, Female, Hyperplasia, Male, Obesity, Organ Size, Sex Characteristics, Adipocytes, Adipogenesis, Mice, Adipose Tissue, White, Diet, High-Fat
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