Novel Peptide Involved in Energy Homeostasis

Abstract

The expression of a mRNA encoding a putative 76 amino acid, secreted protein (“Enho1”) was found to negatively correlate with fasting triglyceride and cholesterol levels. A recombinant adenovirus was used to increase the expression of Enho1 mRNA in two mouse models of obesity, KK-A y and Lep ob /Lep ob mice. Over-expression of Enho1 by adenovirus injection significantly, and reproducibly, reduced fasting triglyceride and cholesterol levels in both models. In addition, transgenic mice strains were made that over express Enho1 protein. Additionally, the expression of a key gene involved in lipogenesis (fatty acid synthase) and FAS protein levels were reduced by ENHO1 adenoviral treatment in Lep ob /Lep ob mice. Full-length ENHO1 peptide, or peptide derivatives, homologues, analogues, or mimetics thereof, delivered by oral intake, injection, subcutaneous patch, or intranasal routes, could be used as therapeutic or diagnostic agents for hypercholesterolemia, hypertriglyceridemia, insulin resistance, obesity, diabetes, and/or energy imbalance.

What is claimed: 
     
         1 . A Enho1 peptide, wherein the sequence of the Enho1 peptide is a sequence selected from the group consisting of SEQ ID NO: 10 and SEQ ID NO:11. 
     
     
         2 . The peptide of  claim 1 , wherein the sequence is SEQ ID NO: 10. 
     
     
         3 . The peptide of  claim 1 , wherein the sequence is SEQ ID NO: 11. 
     
     
         4 . The peptide of  claim 1 , wherein the peptide is a mammalian peptide. 
     
     
         5 . The peptide of  claim 1 , wherein the peptide is a human peptide. 
     
     
         6 . The peptide of  claim 1 , wherein the peptide is a murine peptide. 
     
     
         7 . The peptide of  claim 1 , wherein the peptide is a synthetic peptide. 
     
     
         8 . An antibody, and fragments, derivatives, homologs and analogs thereof, which immunospecifically binds to the peptide of  claim 1 . 
     
     
         9 . An antibody of  claim 8  labeled with a detectable label. 
     
     
         10 . An antibody or fragment of  claim 8 , wherein the antibody is a polyclonal antibody. 
     
     
         11 . An antibody or fragment of  claim 8 , wherein the antibody is a monoclonal antibody. 
     
     
         12 . A pharmaceutical composition comprising an Enho1 peptide of  claim 1 , and a pharmaceutical acceptable carrier. 
     
     
         13 . The pharmaceutical composition of  claim 8 , additionally comprising a compound selected from the group consisting of leptin and adiponectin.