Novel Peptides 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 . An Enho1 peptide, wherein said Enho1 peptide consists essentially of the 43-amino acid peptide whose sequence consists of SEQ ID NO: 10, or said Enho1 peptide consists essentially of the 38-amino acid peptide whose sequence consists of SEQ ID NO: 11. 
     
     
         2 . The peptide of  claim 1 , wherein said peptide consists essentially of the 43-amino-acid peptide whose sequence consists of SEQ ID NO: 10. 
     
     
         3 . The peptide of  claim 1 , wherein said peptide consists essentially of the 38-amino-acid peptide whose sequence consists of SEQ ID NO: 11. 
     
     
         4 . A pharmaceutical composition comprising a therapeutically effective amount of the peptide of  claim 2 , and a pharmaceutically acceptable carrier. 
     
     
         5 . The pharmaceutical composition of  claim 4 , additionally comprising a compound selected from the group consisting of leptin and adiponectin. 
     
     
         6 . A pharmaceutical composition comprising a therapeutically effective amount of the peptide of  claim 3 , and a pharmaceutically acceptable carrier. 
     
     
         7 . The pharmaceutical composition of  claim 6 , additionally comprising a compound selected from the group consisting of leptin and adiponectin.