A soluble activin receptor type IIb prevents the effects of androgen deprivation on body composition and bone health
| Autor: | Jasbir Seehra, Ben Umiker, Joseph Barberio, Kathryn W. Underwood, Jeffrey A. Ucran, Alan Koncarevic, June Liu, Katia Liharska, Matthew S. Spaits, Jennifer Lachey, Monique V. Davies, Scott Pearsall, Kathleen N. Tomkinson, Ravindra Kumar, Theresa Baker, Abigail Pullen, Travis E. Monnell, Elizabeth Howard, Sako Dianne S, Milton Cornwall-Brady, Asya Grinberg |
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| Rok vydání: | 2010 |
| Předmět: |
Leptin
Male medicine.medical_specialty medicine.drug_class medicine.medical_treatment Activin Receptors Type II Recombinant Fusion Proteins Adipose tissue Biology Cell Line Mice Random Allocation Endocrinology In vivo Bone Density Internal medicine medicine Animals Humans Orchiectomy Obesity Muscle Skeletal Analysis of Variance Adiponectin Insulin Body Weight Androgen Antagonists Activin receptor Androgen Immunoglobulin Fc Fragments Mice Inbred C57BL Adipose Tissue Solubility Immunoglobulin G Systemic administration Body Composition |
| Zdroj: | Endocrinology. 151(9) |
| ISSN: | 1945-7170 |
| Popis: | Androgen deprivation, a consequence of hypogonadism, certain cancer treatments, or normal aging in men, leads to loss of muscle mass, increased adiposity, and osteoporosis. In the present study, using a soluble chimeric form of activin receptor type IIB (ActRIIB) we sought to offset the adverse effects of androgen deprivation on muscle, adipose tissue, and bone. Castrated (ORX) or sham-operated (SHAM) mice received either TBS [vehicle-treated (VEH)] or systemic administration of ActRIIB-mFc, a soluble fusion protein comprised of a form of the extracellular domain of ActRIIB fused to a murine IgG2aFc subunit. In vivo body composition imaging demonstrated that ActRIIB-mFc treatment results in increased lean tissue mass of 23% in SHAM mice [19.02 ± 0.42 g (VEH) versus 23.43 ± 0.35 g (ActRIIB-mFc), P < 0.00001] and 26% in ORX mice [15.59 ± 0.26 g (VEH) versus 19.78 ± 0.26 g (ActRIIB-mFc), P < 0.00001]. Treatment also caused a decrease in adiposity of 30% in SHAM mice [5.03 ± 0.48 g (VEH) versus 3.53 ± 0.19 g (ActRIIB-mFc), NS] and 36% in ORX mice [7.12 ± 0.53 g (VEH) versus 4.57 ± 0.28 g (ActRIIB-mFc), P < 0.001]. These changes were also accompanied by altered serum levels of leptin, adiponectin, and insulin, as well as by prevention of steatosis (fatty liver) in ActRIIB-mFc-treated ORX mice. Finally, ActRIIB-mFc prevented loss of bone mass in ORX mice as assessed by whole body dual x-ray absorptiometry and micro-computed tomography of proximal tibias. The data demonstrate that treatment with ActRIIB-mFc restored muscle mass, adiposity, and bone quality to normal levels in a mouse model of androgen deprivation, thereby alleviating multiple adverse consequences of such therapy. |
| Databáze: | OpenAIRE |
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