Methods and compositions for treatment of metabolic disorders

Abstract

The present invention relates to the discovery that increases in invariant NKT cell (iNKT) number and/or activity can reduce the incidence or severity of metabolic disorders such as obesity and diabetes. The invention accordingly features methods, kits, and compositions for the treatment of such metabolic disorders by administration of a composition capable of increasing iNKT activity.

What is claimed is: 
     
         1 . A method of treating a subject suffering from a metabolic disorder, said method comprising administering to said subject a sufficient amount of a composition that increases invariant NKT (iNKT) cell activity. 
     
     
         2 . The method of  claim 1 , wherein said composition comprises a glycolipid; an antibody or an antigen-binding fragment thereof; or an iNKT. 
     
     
         3 . The method of  claim 2 , wherein said glycolipid is a bacterial glycolipid capable of activating iNKT. 
     
     
         4 . The method of  claim 2 , wherein said glycolipid is α-galactosylceramide or an analog thereof. 
     
     
         5 . The method of  claim 2 , wherein said antibody or antigen-binding fragment thereof specifically binds to an iNKT and increases activity of said iNKT. 
     
     
         6 . The method of  claim 5 , wherein said antibody or antigen-binding fragment thereof binds to the CDR3 loop or the α-β junction of said iNKT. 
     
     
         7 . The method of  claim 2 , wherein said iNKT is an autologous iNKT. 
     
     
         8 . The method of  claim 1 , wherein said composition further comprises a pharmaceutically acceptable carrier or wherein said composition is administered intravenously, intramuscularly, orally, by inhalation, parenterally, intraperitoneally, intraarterially, transdermally, sublingually, nasally, transbuccally, liposomally, adiposally, ophthalmically, intraocularly, subcutaneously, intrathecally, topically, or locally. 
     
     
         9 . (canceled) 
     
     
         10 . A method for treating a subject suffering from a metabolic disorder, said method comprising the steps:
 (a) obtaining a biological sample from said subject, said sample containing a population of iNKT;   (b) contacting said sample with a sufficient amount of an agent capable of selectively expanding said iNKT; and   (c) administering said iNKT of step (b) to said subject in an amount sufficient to treat said metabolic disorder.   
     
     
         11 . The method of  claim 10 , wherein said biological sample is a blood sample. 
     
     
         12 . The method of  claim 10 , wherein said agent is a glycolipid or said agent is an antibody or an antigen-binding fragment thereof. 
     
     
         13 . The method of  claim 12 , wherein said glycolipid is a bacterial glycolipid capable of activating iNKT. 
     
     
         14 . The method of  claim 12 , wherein said glycolipid is α-galactosylceramide or an analog thereof. 
     
     
         15 . The method of  claim 12 , wherein said antibody or antigen-binding fragment thereof specifically binds to an iNKT and increases activity of said iNKT. 
     
     
         16 . The method of  claim 15 , wherein said antibody or antigen-binding fragment thereof binds to the CDR3 loop or the α-β junction of said iNKT. 
     
     
         17 . The method of  claim 10 , wherein said iNKT is administered intravenously, intramuscularly, orally, by inhalation, parenterally, intraperitoneally, intraarterially, transdermally, sublingually, nasally, transbuccally, liposomally, adiposally, opthalmically, intraocularly, subcutaneously, intrathecally, topically, or locally. 
     
     
         18 . The method of  claim 1 , wherein said metabolic disorder is diabetes, obesity, diabetes as a consequence of obesity, hyperglycemia, dyslipidemia, hypertriglyceridemia, syndrome X, insulin resistance, impaired glucose tolerance (IGT), diabetic dyslipidemia, hyperlipidemia, a cardiovascular disease, or hypertension. 
     
     
         19 . The method of  claim 18 , wherein said diabetes is type I diabetes or type II diabetes. 
     
     
         20 . The method of  claim 1 , wherein said subject is a human. 
     
     
         21 . (canceled) 
     
     
         22 . A kit comprising:
 (a) a composition that increases iNKT activity; and p 1  (b) a therapeutic for treating a metabolic disorder.   
     
     
         23 . A composition comprising:
 (a) a first agent that increases iNKT activity; and   (b) a second agent for treating a metabolic disorder, wherein said agents are together present in an amount sufficient to treat said metabolic disorder.   
     
     
         24 . The method of  claim 10 , wherein said metabolic disorder is diabetes, obesity, diabetes as a consequence of obesity, hyperglycemia, dyslipidemia, hypertriglyceridemia, syndrome X, insulin resistance, impaired glucose tolerance (IGT), diabetic dyslipidemia, hyperlipidemia, a cardiovascular disease, or hypertension.