Methods of modulating lipid metabolism and storage

Abstract

Anti-hedgehog antibodies directed at blocking the binding of hedgehog to its receptor patched-1, will impair lipid metabolism and storage. This invention presents methods for the treatment of a variety of lipid metabolism and lipid storage disorders, aberrant apolipoprotein expression, atherosclerosis and other lipid associated disorders using lipid modulators such as hedgehog antagonists or hedgehog agonists.

1 . A method for modulating lipid metabolism in an animal comprising the step of administering a pharmaceutically effective amount of a lipid modulator selected from the group consisting of: 
 (a) a hedgehog antagonist; and    (b) a hedgehog agonist.    
     
     
         2 . A method of modulating vacuole formation in intestinal epithelial cells in an animal comprising the step of administering to the cell a pharmaceutically effective amount of a lipid modulator selected from the group consisting of: 
 (a) a hedgehog, antagonist; and    (b) a hedgehog agonist.    
     
     
         3 . A method for modulating the accumulation of fat in intestinal epithelial cells in an animal comprising the step of administering a pharmaceutically effective amount of a lipid modulator selected from the group consisting of: 
 (a) a hedgehog antagonist; and    (b) a hedgehog agonist.    
     
     
         4 . A method of treating a cholesterol disorder in an animal comprising the step of administering a pharmaceutically effective amount of a lipid modulator selected from the group consisting of: 
 (a) a hedgehog antagonist; and    (b) a hedgehog agonist.    
     
     
         5 . A method of treating a lipid metabolism disorder in an animal comprising the step of administering a pharmaceutically effective amount of a lipid modulator selected from the group consisting of: 
 (a) a hedgehog antagonist; and    (b) a hedgehog agonist.    
     
     
         6 . The method according to  claim 5 , wherein the lipid metabolism disorder is selected from the group consisting of: 
 (a) a lipid storage disorder;    (b) a lipid transport disorder;    (c) an apolipoprotein disorder;    (d) a triglyceride disorder;    (e) diet-induced hypercholesterolemia;    (f) hypercholesterolemia;    (g) abetalipoproteinemia;    (h) hypobetalipoproteinemia;    (i) a chylomicron-rention disorder;    (j) Anderson's disease;    (k) a fat absorption disorder;    (l) normotriglyceridemic abetalipoproteinemia;    (m) an apo-B 100 deficiency;    (n) a fat soluble vitamin disorder; and    (o) Atherosclerosis.    
     
     
         7 . The method according to  claim 6 , wherein the fat absorption disorder is obesity.  
     
     
         8 . The method according to  claim 6 , wherein the fat absorption disorder is associated with weight loss.  
     
     
         9 . The method according to  claim 6 , wherein the fat soluble vitamin is vitamin A.  
     
     
         10 . The method according to  claim 6 , wherein the fat soluble vitamin is vitamin E.  
     
     
         11 . The method according to  claim 6 , wherein the triglyceride disorder is selected from the group consisting of: 
 (a) a triglyceride metabolism disorder;    (b) a triglyceride transport disorder; and    (c) a triglyceride storage disorder.    
     
     
         12 . The method according to any one of claims  1 - 11 , wherein the hedgehog antagonist binds to the hedgehog receptor, but does not elicit a response, and is selected from the group consisting of: 
 (a) a hedgehog mimetic, or an active fragment thereof;    (b) a modified hedgehog protein, or an active fragment thereof; and    (c) an anti-hedgehog homolog.    
     
     
         13 . The method of  claim 12 , wherein the anti-hedgehog homolog is selected from the group consisting of: 
 (a) a human antibody or an active fragment thereof;    (b) a chimeric antibody or an active fragment thereof; and    (c) a humanized antibody or an active fragment thereof.    
     
     
         14 . The method according to any one of claims  1 - 11 , wherein the hedgehog antagonist is an inactive hedgehog variant that binds to a hedgehog receptor but does not elicit a hedgehog-mediated signaling.  
     
     
         15 . The method according to any one of claims  1 - 11 , wherein the animal is a mammal.  
     
     
         16 . The method according to  claim 15 , wherein the mammal is a human.