Compositions and Methods for Identifying and Modulating Metabolic Health

Abstract

This invention provides reagents, methods and biochemical markers for identifying and providing therapeutic intervention for individuals with metabolic dysfunction, or individuals at risk for metabolic dysfunction.

1 . A method of treating metabolic dysfunction in a subject comprising administering to the subject a therapeutically effective amount of a molecule, wherein said molecule is capable of modulating an intracellular pathway mediated by PLXND1. 
     
     
         2 . The method of  claim 1 , wherein the molecule is a small molecule chemical compound, a nucleic acid molecule, a peptide, or a polypeptide. 
     
     
         3 . (canceled) 
     
     
         4 . (canceled) 
     
     
         5 . The method of  claim 1 , wherein the molecule directly modulates any of the genes, or gene products, for PLXND1, COL5A1, COL1A2, COL2A1, COL4A1, COL5A2, COL5A3, COL6A1, FN1, ACAN, LAMA1, GPC4, or SPARC. 
     
     
         6 . The method of  claim 1 , wherein the molecule is an interfering molecule comprising an antibody, an antibody fragment, an antisense RNA, a cDNA, a dominant-negative form of a molecule, a peptide, or a protein kinase inhibitor. 
     
     
         7 . The method of  claim 1 , wherein the molecule is an agonist. 
     
     
         8 . The method of  claim 1 , wherein the molecule is an antagonist. 
     
     
         9 . (canceled) 
     
     
         10 . The method of  claim 1 , wherein the metabolic dysfunction comprises diabetes, type 2 diabetes, or insulin resistant diabetes. 
     
     
         11 . The method of  claim 1 , is a regulator of extracellular matrix proteins. 
     
     
         12 . (canceled) 
     
     
         13 . A method of identifying a subject at risk for metabolic dysfunction, the method comprising:
 (a) isolating a biosample from a subject;   (b) determining a level of one or more biomarkers present in the biosample;   wherein said one or more biomarkers is:
 PlexinD1 protein or nucleic acid, 
 COL5A 1 protein or nucleic acid, 
 COL1A2, COL2A1, COL4A1, COL5A2, COL5A3, COL6A1, FN1, ACAN, LAMA1, GPC4, or SPARC protein or nucleic acid 
 visceral adipose tissue, 
 subcutaneous adipose tissue, 
 hypertrophic visceral adipose tissue, or 
 hyperplastic visceral adipose tissue; and 
   (c) identifying the subject as having a risk for metabolic dysfunction when the concentration of one or more biomarkers is increased or decreased relative to a control level or range.   
     
     
         14 . The method of  claim 13 , wherein the one or more biomarkers comprises at least two biomarkers. 
     
     
         15 . The method of  claim 13 , wherein the one or more biomarkers comprises a ratio of biomarkers. 
     
     
         16 . The method of  claim 15 , wherein the ratio of biomarkers is comprised of a level of visceral adipose tissue and a level of subcutaneous adipose tissue. 
     
     
         17 . The method of  claim 13 , wherein the metabolic dysfunction comprises a diabetic condition. 
     
     
         18 . The method of  claim 17 , wherein the diabetic condition comprises metabolic syndrome or type 2 diabetes. 
     
     
         19 . (canceled) 
     
     
         20 . The method of  claim 13 , wherein the metabolic dysfunction comprises insulin resistance. 
     
     
         21 . (canceled) 
     
     
         22 . (canceled) 
     
     
         23 . The method of  claim 13 , wherein the biosample is comprised of biopsy material, adipose tissue, bone marrow samples, blood, blood plasma, serum or cellular fraction thereof, urine, feces, saliva, tears, or cells derived from a biological source. 
     
     
         24 . The method of  claim 13 , wherein determining the level of one or more biomarkers comprises PCR, RT-PCR, ELISA, immunolabeling, in situ hybridization, or nucleic acid sequencing. 
     
     
         25 . A method for identifying a subject that is eligible for reimbursement of an insurance claim for treatment of metabolic dysfunction, the method comprising:
 (a) isolating a biosample from a subject;   (b) determining a level of one or more biomarkers present in the biosample;   wherein said one or more biomarkers is selected from:
 PlexinD1 protein or nucleic acid, 
 COL5A1 protein or nucleic acid, 
 COL1A2, COL2A1, COL4A1, COL5A2, COL5A3, COL6A1, FN1, ACAN, LAMA1, GPC4, or SPARC protein or nucleic acid 
 visceral adipose tissue, 
 subcutaneous adipose tissue, 
 hypertrophic visceral adipose tissue, or 
 hyperplastic visceral adipose tissue; and 
   (c) identifying the subject as eligible for reimbursement of the insurance claim when the concentration of one or more biomarkers is increased or decreased relative to an insurance control value.   
     
     
         26 . A method for determining the efficacy of a treatment for metabolic dysfunction in a subject, the method comprising:
 (a) treating a subject for a metabolic dysfunction;   (b) isolating a biosample from the subject;   (c) determining a level of one or more biomarkers present in the biosample;   wherein said one or more biomarkers is selected from:
 PlexinD1 protein or nucleic acid, 
 COL5A 1 protein or nucleic acid, 
 COL1A2, COL2A1, COL4A1, COL5A2, COL5A3, COL6A1, FN1, ACAN, LAMA1, GPC4, or SPARC protein or nucleic acid 
 visceral adipose tissue, 
 subcutaneous adipose tissue, 
 hypertrophic visceral adipose tissue, or 
 hyperplastic visceral adipose tissue; and 
   (d) determining the efficacy of the treatment for metabolic dysfunction when the concentration of one or more biomarkers is increased or decreased relative to a reference level of the one or more biomarkers.   
     
     
         27 . The method of  claim 26 , wherein the reference level of one or more biomarkers is derived from a population of healthy subjects. 
     
     
         28 . The method of  claim 26 , wherein the reference level of one or more biomarkers is derived from a biosample isolated from the subject prior to treating the subject for a metabolic dysfunction.