A PRDM16-driven signal regulates body composition in testosterone-treated hypogonadal men.
PRDM16
adipogenesis
estrogen
myogenesis
testosterone
Journal
Frontiers in endocrinology
ISSN: 1664-2392
Titre abrégé: Front Endocrinol (Lausanne)
Pays: Switzerland
ID NLM: 101555782
Informations de publication
Date de publication:
2024
2024
Historique:
received:
30
04
2024
accepted:
13
08
2024
medline:
17
9
2024
pubmed:
17
9
2024
entrez:
17
9
2024
Statut:
epublish
Résumé
Testosterone (T) therapy increases lean mass and reduces total body and truncal fat mass in hypogonadal men. However, the underlying molecular mechanisms for the reciprocal changes in fat and lean mass in humans are not entirely clear. Secondary analysis of specimens obtained from a single-arm, open-label clinical trial on pharmacogenetics of response to T therapy in men with late-onset hypogonadism, conducted between 2011 and 2016 involving 105 men (40-74 years old), who were given intramuscular T cypionate 200 mg every 2 weeks for 18 months. Subcutaneous fat (SCF), peripheral blood mononuclear cells (PBMC) and serum were obtained from the participants at different time points of the study. We measured transcription factors for adipogenesis and myogenesis in the SCF, and PBMC, respectively, by real-time quantitative PCR at baseline and 6 months. Serum levels of FOLLISTATIN, PAX7, MYOSTATIN, ADIPSIN, and PRDM16 were measured by ELISA. As expected, there was a significant increase in T and estradiol levels after 6 months of T therapy. There was also a reduction in fat mass and an increase in lean mass after 6 months of T therapy. Gene-protein studies showed a significant reduction in the expression of the adipogenic markers Our study supports that molecular shift from the adipogenic to the myogenic pathway in men with hypogonadism treated with T could be mediated directly or indirectly by enhanced PRDM16 activity, in turn a result from increased estradiol level. This might have led to the reduction in body fat and increase in lean mass commonly seen in hypogonadal men treated with T.
Sections du résumé
Background
UNASSIGNED
Testosterone (T) therapy increases lean mass and reduces total body and truncal fat mass in hypogonadal men. However, the underlying molecular mechanisms for the reciprocal changes in fat and lean mass in humans are not entirely clear.
Methods
UNASSIGNED
Secondary analysis of specimens obtained from a single-arm, open-label clinical trial on pharmacogenetics of response to T therapy in men with late-onset hypogonadism, conducted between 2011 and 2016 involving 105 men (40-74 years old), who were given intramuscular T cypionate 200 mg every 2 weeks for 18 months. Subcutaneous fat (SCF), peripheral blood mononuclear cells (PBMC) and serum were obtained from the participants at different time points of the study. We measured transcription factors for adipogenesis and myogenesis in the SCF, and PBMC, respectively, by real-time quantitative PCR at baseline and 6 months. Serum levels of FOLLISTATIN, PAX7, MYOSTATIN, ADIPSIN, and PRDM16 were measured by ELISA.
Results
UNASSIGNED
As expected, there was a significant increase in T and estradiol levels after 6 months of T therapy. There was also a reduction in fat mass and an increase in lean mass after 6 months of T therapy. Gene-protein studies showed a significant reduction in the expression of the adipogenic markers
Conclusion
UNASSIGNED
Our study supports that molecular shift from the adipogenic to the myogenic pathway in men with hypogonadism treated with T could be mediated directly or indirectly by enhanced PRDM16 activity, in turn a result from increased estradiol level. This might have led to the reduction in body fat and increase in lean mass commonly seen in hypogonadal men treated with T.
Identifiants
pubmed: 39286266
doi: 10.3389/fendo.2024.1426175
pmc: PMC11402695
doi:
Substances chimiques
Testosterone
3XMK78S47O
Transcription Factors
0
DNA-Binding Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1426175Informations de copyright
Copyright © 2024 Bathina, Colleluori, Villareal, Aguirre, Chen and Armamento-Villareal.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.