Compositions and Methods for Induced Brown Fat Differentiation

Abstract

The invention provides methods and compositions for inducing brown fat cell differentiation through modulation of both Prdm1β and C/EBPβ activity and/or expression. Also provided are methods for preventing or treating obesity or an obesity related disorder in a subject through stimulation of both Prdm1β and C/EBPβ expression and/or activity. Further provided are methods for identifying compounds that are capable of modulating both Prdm1β and C/EBPβ expression and/or activity.

1 . A method for preventing or treating obesity or an obesity-related disorder in a subject comprising inducing both Prdm16 and C/EBPβ expression and/or activity sufficient to activate brown fat cell differentiation, wherein the differentiated brown fat cells increase energy expenditure to thereby prevent or treat obesity or an obesity-related disorder in the subject. 
     
     
         2 . The method of  claim 1 , where in the obesity-related disorder is selected from the group consisting of: insulin resistance, type II diabetes, hypertension, hyperuricemia, fatty liver, non-alcoholic fatty liver disease, polycystic ovarian syndrome, acanthosis nigricans, hyperphagia, endocrine abnormalities, triglyceride storage disease, Bardet-Biedl syndrome, Lawrence-Moon syndrome, Prader-Labhart-Willi syndrome, anorexia, and cachexia. 
     
     
         3 . The method of  claim 1 , wherein the obesity-related disorder is Type II diabetes. 
     
     
         4 . The method of  claim 1 , wherein the subject is human. 
     
     
         5 . A method for increasing energy expenditure in a mammal comprising inducing both Prdm16 and C/EBPβ expression and/or activity sufficient to activate brown fat cell differentiation in the mammal, wherein the differentiated brown fat cells promote energy expenditure thereby increasing energy expenditure in the mammal. 
     
     
         6 . The method of  claim 5 , wherein the mammal is a human. 
     
     
         7 . A method for treating obesity or an obesity-related disorder in a subject comprising administering to the subject an agent that induces expression and/or activity of both Prdm16 and C/EBPβ, wherein Prdm16 and C/EBPβ expression and/or activity increases respiration and energy expenditure to thereby treat obesity or an obesity-related disorder in the subject. 
     
     
         8 . The method of  claim 7 , wherein the respiration is total respiration or uncoupled respiration. 
     
     
         9 . The method of  claim 7 , wherein the respiration is assessed using positron emission tomography. 
     
     
         10 . The method of  claim 7 , where in the obesity-related disorder is selected from the group consisting of: insulin resistance, type II diabetes, hypertension, hyperuricemia, fatty liver, non-alcoholic fatty liver disease, polycystic ovarian syndrome, acanthosis nigricans, hyperphagia, endocrine abnormalities, triglyceride storage disease, Bardet-Biedl syndrome, Lawrence-Moon syndrome, Prader-Labhart-Willi syndrome, anorexia, and cachexia. 
     
     
         11 . The method of  claim 7 , wherein the obesity-related disorder in Type II diabetes. 
     
     
         12 . The method of  claim 7 , wherein the subject is a human. 
     
     
         13 - 50 . (canceled)