Methods for increasing thermogenic adipocytes

Abstract

In certain aspects, the present invention provides compositions and methods for increasing thermogenic adipocytes (e.g., brown adipocytes or other UCP-1 expressing adipocytes) by administering an antagonist of an ActRIIB signaling pathway. Examples of such antagonists include ActRIIB polypeptides, anti-ActRIIB antibodies, anti-myostatin antibodies, anti-GDF3 antibodies, anti-Nodal, anti-activin, and anti-GDF11 antibodies. A variety of metabolic and other disorders may be treated by causing an increase in thermogenic adipocytes.

1 - 10 . (canceled) 
     
     
         11 . A method for increasing thermogenic adipocytes in a patient in need thereof, the method comprising administering an effective amount of a polypeptide comprising an amino acid sequence that is at least 95% identical to the sequence of amino acids 29-109 of SEQ ID NO: 2, wherein administration of the polypeptide increases SIRT-1 and/or PGC-1α mRNA levels in adipocytes of the treated patient. 
     
     
         12 . The method of  claim 11 , wherein the polypeptide is a fusion protein comprising a portion heterologous to ActRIIB. 
     
     
         13 . The method of  claim 12 , wherein the polypeptide is fused to a constant domain of an immunoglobulin. 
     
     
         14 . The method of  claim 12 , wherein the polypeptide is fused to an Fc portion of an immunoglobulin. 
     
     
         15 . The method of  claim 14 , wherein the immunoglobulin is a human IgG1. 
     
     
         16 . The method of  claim 11 , wherein the polypeptide is a dimer. 
     
     
         17 . The method of  claim 11 , wherein the polypeptide comprises the sequence of SEQ ID NO: 5. 
     
     
         18 . The method of  claim 11 , wherein the polypeptide comprises an amino acid sequence that is at least 97% identical to the sequence of amino acids 29-109 of SEQ ID NO: 2. 
     
     
         19 . The method of  claim 11 , wherein the polypeptide comprises an amino acid sequence that is at least 90% identical to the sequence of amino acids 25-131 of SEQ ID NO: 2. 
     
     
         20 . The method of  claim 19 , wherein the polypeptide comprises an amino acid sequence that is at least 95% identical to the sequence of amino acids 25-131 of SEQ ID NO: 2. 
     
     
         21 . The method of  claim 20 , wherein the polypeptide comprises an amino acid sequence that is at least 97% identical to the sequence of amino acids 25-131 of SEQ ID NO: 2. 
     
     
         22 . The method of  claim 11 , wherein administration of the polypeptide increases SIRT-1 mRNA levels in adipocytes of the treated patient. 
     
     
         23 . The method of  claim 11 , wherein administration of the polypeptide increases PGC-1α mRNA levels in adipocytes of the treated patient. 
     
     
         24 . The method of  claim 11 , wherein administration of the polypeptide increases SIRT-1 and PGC-1α mRNA levels in adipocytes of the treated patient. 
     
     
         25 . The method of  claim 11 , wherein administration of the compound promotes uncoupling protein-1 (UCP-1) expression in adipocytes of the treated patient. 
     
     
         26 . The method of  claim 11 , wherein the polypeptide comprises the sequence of SEQ ID NO: 6.