Ucp1 (thermogenin) - inducing agents for use in the treatment of a disorder of the energy homeostasis

Abstract

The present invention relates to compositions comprising an agent, like a polynucleotide, which induces or upregulates expression of UCP1 for use in treating or preventing a disorder of the energy homeostasis, overweight, adiposity, obesity, metabolic syndrome or related diseases or disorders in a subject. The present invention also relates to a method of treating or preventing a disorder of the energy homeostasis, overweight, adiposity, obesity, metabolic syndrome or related diseases or disorders in a subject comprising administrating a composition comprising a polynucleotide which induces or upregulates expression of UCP1.

1 . A composition comprising an agent which induces or upregulates expression of UCP1 and which negatively interferes concomitantly and independently with at least two UCP1-suppressors and/or suppressors of the UCP1-promoting insulin signalling pathway for use in treating or preventing diseases or disorders of the energy homeostasis or related diseases or disorders in a subject wherein the agent is a polynucleotide comprising at least one non-naturally occurring nucleotide selected from the group consisting of:
 (i) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 1;   (ii) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 2;   (iii) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 3;   (iv) a polynucleotide which is at least 90% identical to any one of (i) to (iii); and   (v) a polynucleotide according to (iv), which comprises the nucleotide sequence of SEQ ID NO: 6.   
     
     
         2 .- 5 . (canceled) 
     
     
         6 . The composition of claim  4 , wherein said polynucleotide is a microRNA, a precursor of a microRNA, or a mimic microRNA or a precursor thereof. 
     
     
         7 . The composition of claim  4 , wherein said polynucleotide is about 15 to about 100 nucleotides in length. 
     
     
         8 .- 11 . (canceled) 
     
     
         12 . The composition of  claim 1 , wherein said polynucleotide or a nucleotide sequence encoding said polynucleotide is cloned into a vector. 
     
     
         13 . The composition of  claim 12 , wherein said vector is transduced, transformed or transfected into a cell. 
     
     
         14 . The composition of  claim 1 , further comprising a pharmaceutically acceptable carrier. 
     
     
         15 .- 17 . (canceled) 
     
     
         18 . The composition of  claim 1 , wherein the at least one non-naturally occurring nucleotide is a peptide nucleic acid (PNA), a glycol nucleic acid (GNA), a threose nucleic acid (TNA), a locked nucleic acid (LNA), an oligonucleotide thiophosphate, a substituted ribo-oligonucleotides, a morpholino polynucleotide, or an antagomir polynucleotide.