Possible Mechanism For Anrogenic Fat Loss  

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jboldman
(@jboldman)
Reputable Member
Joined: 6 months ago
Posts: 359
29/08/2018 5:02 am  

WHile it is commonly accepted that Testosterone supplementation leads to fat loss, this is a possible mechanism to explain that fat loss.

jb

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Testosterone Inhibits Adipogenic Differentiation in 3t3-L1 Cells: Nuclear Translocation of Androgen Receptor Complex with {beta}-Catenin and TCF4 may Bypass Canonical Wnt Signaling to Downregulate Adipogenic Transcription Factors
Rajan Singh*, Jorge N. Artaza, Wayne E. Taylor, Melissa Braga, Xin Yuan, Nestor F. Gonzalez-Cadavid, and Shalender Bhasin

Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, CA 90059; Beth Israel Deaconess Medical Center and Harvard Medical School, Boston; Section of Endocrinology, Diabetes, and Nutrition, Boston Medical Center

Testosterone supplementation in men decreases fat mass; however, the mechanisms by which it inhibits fat mass are unknown. We hypothesized that testosterone inhibits adipogenic differentiation of preadipocytes by activation of androgen receptor (AR)/{beta}-catenin interaction, and subsequent translocation of this complex to the nucleus thereby bypassing canonical Wnt signaling. We tested this hypothesis in 3T3-L1 cells that differentiates to form fat cells in adipogenic medium. We found that these cells express androgen receptor (AR), and testosterone and dihydrotestosterone dose-dependently inhibited adipogenic differentiation as analyzed by Oil-Red O staining, and down regulation of C/EBP-{alpha} and -{delta} and PPAR{gamma}2 protein and mRNA. These inhibitory effects of androgens were partially blocked by flutamide or bicalutamide. Androgen treatment was associated with nuclear translocation of {beta}-catenin and AR. Immunoprecipitation studies demonstrated association of {beta}-catenin with AR and T-cell factor 4 (TCF4) in the presence of androgens. Transfection of TCF4 cDNA inhibited adipogenic differentiation; whereas, a dominant negative TCF4 cDNA construct induced adipogenesis and blocked testosterone's inhibitory effects. Our gene array analysis indicates that testosterone treatment led to activation of some Wnt target genes. Expression of constitutively activated AR fused with VP16 did not inhibit the expression of C/EBP-{alpha} in the absence of androgens. Conclusions: Testosterone and dihydrotestosterone inhibit adipocyte differentiation in vitro through an AR-mediated nuclear translocation of {beta}-catenin and activation of downstream Wnt signaling. These data provide evidence for a regulatory role for androgens in inhibiting adipogenic differentiation, and a mechanistic explanation consistent with the observed reduction in fat mass in men treated with androgens.


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liftsiron
(@liftsiron)
Estimable Member
Joined: 6 months ago
Posts: 199
29/08/2018 5:03 am  

Nice find jb.

liftsiron is a fictional character and should be taken as such.


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Neuromancer
(@neuromancer)
Active Member
Joined: 4 months ago
Posts: 5
29/08/2018 5:04 am  

Good find indeed JB.


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