Methods for increasing adiponectin
In certain aspects, the present invention provides compositions and methods for increasing adiponectin in a patient in need thereof by administering an antagonist of an ActRIIB signaling pathway. Examples of such antagonists include ActRIIB polypeptides, anti-ActRIIB antibodies, anti-activin A and/or B antibodies, anti-myostatin antibodies, anti-GDF3 antibodies, and anti-BMP7 antibodies. Also provided are methods for ameliorating one or more undesired effects of anti-androgen therapy, including muscle loss, bone loss, increased adiposity, and/or increased insulin resistance. A variety of disorders may be treated by causing an increase in circulating adiponectin concentrations.
1. A method for increasing adiponectin in a patient in need thereof, the method comprising administering an effective amount of an antibody, or antigen-binding fragment thereof, that specifically binds to an activin type IIB receptor (ActRIIB), and wherein the antibody, or antigen-binding fragment thereof, inhibits one or more of activin A, GDF8, and GDF11 from binding to the ActRIIB.
2. The method of claim 1 , wherein the antibody, or antigen-binding fragment thereof, binds to a soluble ActRIIB peptide.
3. The method of claim 1 , wherein the antibody, or antigen-binding fragment thereof, is monoclonal.
4. The method of claim 1 , wherein the antibody, or antigen-binding fragment thereof, is chimeric.
5. The method claim 1 , wherein the antibody, or antigen-binding fragment thereof, is humanized.
6. The method of claim 1 , wherein the antibody, or antigen binding fragment thereof, is selected from: a single chain antibody, a bispecific antibody, a F(ab) 2 fragment, and a Fab′ fragment.
7. The method of claim 1 , wherein the patient has adiponectin deficiency or insufficiency.
8. The method of claim 1 , wherein the patient has low circulating concentrations of adiponectin.
9. The method of claim 1 , wherein administration of the antibody, or antigen-binding fragment thereof, increases adiponectin expression in adipocytes of the treated patient.
10. The method of claim 1 , wherein the antibody, or antigen-binding fragment thereof, inhibits activin A from binding to the ActRIIB.
11. The method of claim 1 , wherein the antibody, or antigen-binding fragment thereof, inhibits GDF8 from binding to the ActRIIB.
12. The method of claim 1 , wherein the antibody, or antigen-binding fragment thereof, inhibits GDF11 from binding to the ActRIIB.