Lipoprotein-Regulating Medicaments

Abstract

Methods and pharmaceutical compositions useful for treating obesity-related disorders using ApM-1 and related proteins.

1 . A method of using an agent which influences the partitioning of dietary lipids between the liver and peripheral tissues for use as a medicament to treat a condition in which it is desirable to increase the partitioning of dietary lipids to the liver, reducing the levels of free fatty acids in obese individuals, decreasing the body weight of obese individuals, or treating an obesity related condition selected from the group consisting of obesity-related atherosclerosis, obesity-related insulin resistance, obesity-related hypertension, microangiopathic lesions resulting from obesity-related Type II diabetes, ocular lesions caused by microangiopathy in obese individuals with Type II diabetes, and renal lesions caused by microangiopathy in obese individuals with Type II diabetes. 
     
     
         2 . An isolated polypeptide comprising a consensus sequence selected from the group consisting of SEQ ID NO: 1 and SEQ ID NO:2. 
     
     
         3 . The isolated polypeptide according to  claim 2 , wherein said compound comprises a polypeptide selected from the group consisting of C1q, AdipoQ, ApM1, Acrp 30, cerebellin, multimerin and fragments of any of these polypeptides. 
     
     
         4 . The isolated polypeptide according to  claim 3 , wherein said polypeptide is a human polypeptide and is selected from the group consisting of ApM1 and fragments of ApM1. 
     
     
         5 . A method of reducing plasma lipoprotein or triglyceride in an animal, comprising the steps of:
 identifying an animal having a measurable plasma lipoprotein or plasma triglyceride level; and   administering to said animal a composition that includes a pharmaceutically acceptable carrier and an ApM1, Adipo Q or ACRP30 polypeptide comprising the amino acid sequence of SEQ ID: 11, 12, or 13, wherein said polypeptide reduces plasma lipoprotein levels.   
     
     
         6 . A method of identifying candidate pharmaceutical agents for reducing plasma triglyceride levels in an animal, comprising the steps of:
 identifying a compound that comprises a consensus sequence selected from the group consisting of SEQ ID NO: 1 and SEQ ID NO:2;   obtaining a test animal having an initial level of plasma triglycerides;   administering said compound to the test animal;   waiting for a period of time;   measuring a post-treatment level of plasma triglycerides in a blood sample obtained from the test animal; and   identifying as candidate pharmaceutical agents any compound that results in a post-treatment level of plasma triglycerides that is lower than said initial level.   
     
     
         7 . The method according to  claim 6 , wherein the test animal is a mammal. 
     
     
         8 . The method according to  claim 7 , further comprising the step of feeding a high-fat meal to the mammal. 
     
     
         9 . A method for determining whether an obese individual is at risk of suffering from a condition selected from the group consisting of a condition associated with a lower than desirable level of portioning of dietary lipids to the liver, obesity-related atherosclerosis, obesity-related insulin resistance, obesity-related hypertension, microangiopathic lesions resulting from obesity-related Type II diabetes, ocular lesions caused by microangiopathy in obese subjects with Type II diabetes, and renal lesions caused by microangiopathy in obese subjects with Type II diabetes, comprising the step of determining whether the individual has a lower that normal level of adipoQ activity, ApM1 activity, or activity of a compound analogous thereto. 
     
     
         10 . A method for decreasing the body weight of an individual, increasing the partitioning of lipids to the liver of an individual, or reducing the levels of plasma free fatty acids in an individual, comprising the administration of an effective amount of a composition comprising an Apm1 polypeptide fragment consisting of SEQ ID NO: 11 to said individual. 
     
     
         11 . The method according to  claim 10 , wherein said method is decreasing the body weight of an individual. 
     
     
         12 . The method according to  claim 10 , wherein said method is increasing the partitioning of lipids to the liver of an individual. 
     
     
         13 . The method according to  claim 10 , wherein said method is reducing the levels of plasma free fatty acids in an individual.