Myocyte androgen receptors increase metabolic rate and improve body composition by reducing fat mass.
Testosterone and other androgens are thought to increase lean body mass and reduce fat body mass in men by activating the androgen receptor. However, the clinical potential of androgens for improving body composition is hampered by our limited understanding of the tissues and cells that promote such changes. Here we show that selective overexpression of androgen receptor in muscle cells (myocytes) of transgenic male rats both increases lean mass percentage and reduces fat mass. Similar changes in body composition are observed in human skeletal actin promoter driving expression of androgen receptor (HSA-AR) transgenic mice and result from acute testosterone treatment of transgenic female HSA-AR rats. These shifts in body composition in HSA-AR transgenic male rats are associated with hypertrophy of type IIb myofibers and decreased size of adipocytes. Metabolic analyses of transgenic males show higher activity of mitochondrial enzymes in skeletal muscle and increased O(2) consumption by the rats. These results indicate that androgen signaling in myocytes not only increases muscle mass but also reduces fat body mass, likely via increases in oxidative metabolism.
Fernando
Shannon M
SM
Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada M5S 3G3.
Rao
Pengcheng
P
Niel
Lee
L
Chatterjee
Diptendu
D
Stagljar
Marijana
M
Monks
D Ashley
DA
D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D030801:Animals, Genetically Modified; D001823:Body Composition / Q000187:drug effects / Q000235:genetics*; D002151:Calorimetry; D004734:Energy Metabolism / Q000187:drug effects / Q000235:genetics*; D005260:Female; D006801:Humans; D006984:Hypertrophy / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D032342:Muscle Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism; D009210:Myofibrils / Q000187:drug effects / Q000235:genetics; D010101:Oxygen Consumption / Q000187:drug effects / Q000235:genetics; D051381:Rats; D011944:Receptors, Androgen / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013739:Testosterone / Q000494:pharmacology
D011944:Receptors, Androgen; D013739:Testosterone