Angiopoietin-like protein 8 polypeptide fragments and compositions thereof

Abstract

Methods and compositions for reducing one or more of triglyceride levels, total cholesterol levels and LDL cholesterol levels in a subject are provided. The methods include administering a fragment of ANGPTL8 to a subject having or at risk of developing elevated triglyceride levels, elevated total cholesterol levels and/or elevated LDL cholesterol levels.

1 .- 41 . (canceled) 
     
     
         42 . A polypeptide comprising a fragment of full-length ANGPTL8 (SEQ ID NO:1), wherein the polypeptide comprises the two coiled coil domains of full-length ANGPTL8 and wherein the polypeptide lacks the amino acids 21-70 of full-length ANGPTL8, wherein the polypeptide can decrease triglyceride levels in a human subject. 
     
     
         43 . The polypeptide of  claim 42 , wherein the polypeptide comprises a contiguous amino acid sequence having at least 95% sequence identity to amino acids 80-198 of full-length ANGPTL8. 
     
     
         44 . The polypeptide of  claim 42 , wherein the polypeptide consists of amino acids 80-198 of SEQ ID NO:1. 
     
     
         45 . The polypeptide of  claim 42 , wherein the polypeptide lacks the amino acids 21-80 of full-length ANGPTL8. 
     
     
         46 . The polypeptide of  claim 42 , wherein a heterologous polypeptide is conjugated to the N-terminus or C-terminus of the polypeptide. 
     
     
         47 . The polypeptide of  claim 46 , wherein the heterologous polypeptide is albumin, human serum albumin, or an immunoglobulin Fc. 
     
     
         48 . The polypeptide of  claim 46 , wherein the heterologous polypeptide is conjugated to the polypeptide via a linker sequence. 
     
     
         49 . The polypeptide of  claim 48 , wherein the linker sequence is a cleavable linker sequence or a non-cleavable linker sequence. 
     
     
         50 . A pharmaceutical composition comprising the polypeptide of  claim 42  and a pharmaceutically acceptable carrier. 
     
     
         51 . A polynucleotide that encodes the polypeptide of  claim 42 . 
     
     
         52 . A method of reducing triglyceride levels in a human subject having or at risk of developing elevated triglyceride levels, the method comprising administering to the human subject the polypeptide of  claim 42 . 
     
     
         53 . A method of reducing total cholesterol levels in a human subject having or at risk of developing elevated cholesterol levels, the method comprising administering to the human subject the polypeptide of  claim 42 . 
     
     
         54 . A method of reducing LDL cholesterol levels in a human subject having or at risk of developing elevated LDL cholesterol levels, the method comprising administering to the human subject the polypeptide of  claim 42 .