A Soluble Activin Receptor Type IIB Prevents the Effects of Androgen Deprivation on Body Composition and Bone Health
Abstract
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.
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Systemic administration of ACVR2B/Fc can lead to significant increases in bone density.
“Moreover, because this decoy receptor can block not only MSTN but also activin A, systemic administration of ACVR2B/Fc can also lead to significant increases in bone density (18–20).”
From Targeting myostatin/activin A protects against skeletal muscle and bone loss during spaceflight (2020) · cites this paper as [18]
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- Authors
- Koncarevic, A., Cornwall-Brady, M., Pullen, A., Davies, M., Sako, D., Liu, J., Kumar, R., Tomkinson, K., Baker, T., Umiker, B., Monnell, T., Grinberg, A. V., Liharska, K., Underwood, K. W., Ucran, J. A., Howard, E., Barberio, J., Spaits, M., Pearsall, S., Seehra, J., & Lachey, J.
- Affiliations
- Acceleron Pharma (United States) (US)
- Corresponding author
- Lachey, Jennifer
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2010-07-23
- Volume
- 151
- Issue
- 9
- Pages
- 4289-4300
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2067475521
- Cited by
- 71
- References
- 41
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 2 · 2022: 4 · 2021: 6 · 2020: 8 · 2019: 2 · 2018: 9 · 2017: 6 · 2016: 5 · 2015: 9 · 2014: 1 · 2013: 8 · 2012: 3
- FWCI
- 4.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Acceleron
- 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 › Nutrition and Health in Aging
- Keywords
- ActRIIB, androgen deprivation therapy, castration, muscle mass, lean body mass, adiposity, bone mass, osteoporosis, body composition, leptin, adiponectin, insulin, hepatic steatosis, steatosis, hypogonadism, TGF-beta signaling, TGF-β1, TGF-beta2, TGF-beta3
- MeSH terms
- Adipose Tissue, Analysis of Variance, Androgen Antagonists, Animals, Body Composition, Body Weight, Cell Line, Humans, Immunoglobulin G, Immunoglobulin Fc Fragments, Male, Mice, Inbred C57BL, Obesity, Orchiectomy, Random Allocation, Recombinant Fusion Proteins, Solubility, Bone Density, Muscle, Skeletal, Leptin, Activin Receptors, Type II, Mice
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