Effects of dihydrotestosterone on differentiation and proliferation of human mesenchymal stem cells and preadipocytes
Open accessAbstract
Unlabelled The mechanisms by which androgens regulate fat mass are poorly understood. Although testosterone has been reported to increase lipolysis and inhibit lipid uptake, androgen effects on proliferation and differentiation of human mesenchymal stem cells (hMSCs) and preadipocytes have not been studied. Here, we investigated whether dihydrotestosterone (DHT) regulates proliferation, differentiation, or functional maturation of hMSCs and human preadipocytes from different fat depots. DHT (0-30 nM) dose-dependently inhibited lipid accumulation in adipocytes differentiated from hMSCs and downregulated expression of aP2, PPARgamma, leptin, and C/EBPalpha. Bicalutamide attenuated DHT's inhibitory effects on adipogenic differentiation of hMSCs. Adipocytes differentiated in presence of DHT accumulated smaller oil droplets suggesting reduced extent of maturation. DHT decreased the incorporation of labeled fatty acid into triglyceride, and downregulated acetyl CoA carboxylase and DGAT2 expression in adipocytes derived from hMSCs. DHT also inhibited lipid accumulation and downregulated aP2 and C/EBPalpha in human subcutaneous, mesenteric and omental preadipocytes. DHT stimulated forskolin-stimulated lipolysis in subcutaneous and mesenteric preadipocytes and inhibited incorporation of fatty acid into triglyceride in adipocytes differentiated from preadipocytes from all fat depots.Conclusions DHT inhibits adipogenic differentiation of hMSCs and human preadipocytes through an AR-mediated pathway, but it does not affect the proliferation of either hMSCs or preadipocytes. Androgen effects on fat mass represent the combined effect of decreased differentiation of fat cell precursors, increased lipolysis, and reduced lipid accumulation.
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Testosterone exerts direct effects on adipose tissue by inhibiting adipogenic differentiation of mesenchymal stem cells, reducing lipid accumulation, and stimulating lipolysis through androgen receptor-mediated signalling.
“In addition, testosterone exerts direct effects on adipose tissue by inhibiting the adipogenic differentiation of mesenchymal stem cells, reducing lipid accumulation, and stimulating lipolysis through androgen receptor-mediated signalling [186, 187].”
From Effects of Skeletal Muscle Hypertrophy on Fat Mass and Glucose Homeostasis in Humans and Animals: A Narrative Review with Systematic Literature Search (2025) · cites this paper as [187]
The Abstract and Results §3.3 report that dihydrotestosterone (DHT) inhibited adipogenic differentiation and lipid accumulation in human mesenchymal stem cells, with an androgen-receptor antagonist blocking those effects. Results §3.6 report increased forskolin-induced lipolysis in subcutaneous and mesenteric preadipocytes, but no substantial effect on basal lipolysis. The experiments used DHT rather than testosterone, and the paper does not establish that the lipolysis effect is androgen receptor-mediated. (LLM, conf=0.87)
Experimental — accuracy not yet measuredData obtained from in vitro experiments show that testosterone and DHT can inhibit the differentiation of human and BM-mesenchymal pluripotent cells into adipocytes via AR dependent pathway.
“Data obtained from in vitro experiments show that testosterone and DHT can inhibit the differentiation of human and BM‐mesenchymal pluripotent cells into adipocytes via AR dependent pathway. 110 , 111 , 112 , 113”
From The role of the androgen receptor in the pathogenesis of obesity and its utility as a target for obesity treatments (2022) · cites this paper as [110]
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- Authors
- Gupta, V., Bhasin, S., Guo, W., Singh, R., Miki, R., Chauhan, P., Choong, K., Tchkonia, T., Lebrasseur, N. K., Flanagan, J. N., Hamilton, J. A., Viereck, J. C., Narula, N. S., Kirkland, J. L., & Jasuja, R.
- Affiliations
- Boston University (US)
- Charles R. Drew University of Medicine and Science (US)
- Corresponding author
- Jasuja, Ravi
- ORCID
- Venue
- Molecular and Cellular Endocrinology
- Publisher
- Elsevier BV
- Published
- 2008-12
- Volume
- 296
- Issue
- 1-2
- Pages
- 32-40
- ISSN
- 0303-7207 (ISSN-L)
- PMC
- PMC2873614
- OpenAlex
- W2101395164
- Cited by
- 162
- References
- 57
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 6 · 2023: 9 · 2022: 6 · 2021: 10 · 2020: 10 · 2019: 10 · 2018: 8 · 2017: 14 · 2016: 8 · 2015: 12 · 2014: 6 · 2013: 13 · 2012: 13
- FWCI
- 6.56
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (U01AG014369, R01AG037193, AG 14369, SC1AG033407, SC1AG049682, R01AG014369)
- National Heart, Lung, and Blood Institute (P50HL083801)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK70534, R01DK056891, DK 56891, R01DK049296, R01DK059261, DK-59261, R01DK070534, DK49296)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (U54HD41748, U54HD041748)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- dihydrotestosterone, androgens, mesenchymal stem cells, preadipocytes, adipogenesis, adipocyte proliferation, lipolysis, lipid accumulation, androgen receptor, triglyceride synthesis, fatty acid incorporation, subcutaneous adipose tissue, mesenteric fat, omental fat, bicalutamide, PPARγ, C/EBPα, AP-2
- MeSH terms
- Adult, Animals, Cell Differentiation, Cells, Cultured, Epididymis, Humans, Lipolysis, Male, Mice, Inbred C57BL, Middle Aged, Orchiectomy, Receptors, Androgen, Dihydrotestosterone, Signal Transduction, Adipocytes, Cell Proliferation, Adipogenesis, Mice, Mesenchymal Stem Cells
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