Stem cell activation in adults can reverse detrimental changes in body composition to reduce fat and increase lean mass in both sexes
Open accessAbstract
Detrimental changes in body composition are often associated with declining levels of testosterone. Here, we evaluated the notion that multipotent mesenchymal stem cells, that give rise to both fat and muscle tissue, can play a significant role to alter existing body composition in the adult. Transgenic mice with targeted androgen receptor (AR) overexpression in stem cells were employed. Wild-type littermate and AR-transgenic male and female mice were gonadectomized and left untreated for 2 months. After the hypogonadal period, mice were then treated with 5α-dihydrotestosterone (DHT) for 6 weeks. After orchidectomy (ORX), wild-type males have reduced lean mass and increased fat mass compared to shams. DHT treatment was beneficial to partially restore body composition. In wild-type females, ovariectomy (OVX) produced a similar change but there was no improvement with DHT. In targeted AR transgenic mice, DHT treatment increased lean and reduced fat mass to sham levels. In contrast to wild-type females, DHT treatment in female transgenic mice significantly ameliorated the increased fat and decreased lean mass changes that result after OVX. Our results show that DHT administration reduces fat mass and increases lean mass in wild-type males but not females, indicating that wild-type females are not as sensitive to androgen treatment. Because both male and female transgenic mice are more responsive than wild-type, results suggest that body composition remains linked to stem cell fate in the adult and that targeted androgen signaling in stem cells can play a significant role to reverse detrimental changes in body composition in both sexes.
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DHT treatment was able to reverse the increase in fat accumulation that occurs following gonadectomy in both adult male and female Col3.6AR-Tgs but not WT mice.
“DHT treatment was able to reverse the increase in fat accumulation that occurs following gonadectomy in both adult male and female Col3.6AR‐Tgs but not WT mice.”
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 [158]
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- Authors
- Wiren, K. M., Hashimoto, J. G., & Zhang, X.-W.
- Affiliations
- Oregon Health & Science University (US)
- Corresponding author
- Wiren, Kristine M.
- Venue
- Journal of Cellular Biochemistry
- Publisher
- Wiley
- Published
- 2011-10-22
- Volume
- 112
- Issue
- 12
- Pages
- 3638-3647
- ISSN
- 0730-2312 (ISSN-L)
- PMC
- PMC3202045
- OpenAlex
- W2055393351
- Cited by
- 5
- References
- 50
- Citations by year
- 2024: 1 · 2022: 1 · 2018: 1 · 2016: 1 · 2012: 1
- FWCI
- 0.26
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Cellular Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Defense
- U.S. Department of Veterans Affairs
- U.S. Army
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK067541)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- mesenchymal stem cells, body composition, androgen receptor, dihydrotestosterone, hypogonadism, orchiectomy, ovariectomy, fat mass, lean body mass, sex differences, stem cell fate, transgenic mice, testosterone
- MeSH terms
- Adipose Tissue, Animals, Body Composition, Female, Male, Mice, Transgenic, Muscles, Orchiectomy, Organ Size, Stem Cells, Mice
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