Method for Screening Substance by Measuring PPAR DELTA Activating Effect and Agent

Abstract

The present invention provides a method for screening a substance having a thermogenesis enhancing effect containing a compound having an effect activating PPARδ, an agent containing the compound, and an agent having antidiabetic, antiobestic or visceral accumulated fat-lowering function. The present invention provides an agent containing a compound having an effect activating PPARδ, which is a peroxisome proliferator activated receptor, and having effects which enhances nonshivering thermogenesis (nST), specifically enhances uncoupling respiration in mitochondria of cells in an adipose tissue or the like, or proton leak in inner membranes of mitochondria, and increases the amount of expression of UCP1, and provides an antidiabetic agent, an antiobestic gent and a visceral accumulated fat-lowering agent containing the compound. Further, the present invention provides a method for screening the compound by measuring a PPARδ activating effect.

1 . A method of enhancing thermogenesis effect comprising administering to a subject in need thereof an effective amount of a substance having a PPARδ-activating effect. 
     
     
         2 . A method of enhancing uncoupling respiration in mitochondria comprising administering to a subject in need thereof an effective amount of a substance having a PPARδ-activating effect. 
     
     
         3 . A method of enhancing proton leak in internal membranes of mitochondria comprising administering to a subject in need thereof an effective amount of a substance having a PPARδ-activating effect. 
     
     
         4 . A method of increasing the amount of expression of UCP1 in mitochondria-containing cells comprising administering to a subject in need thereof an effective amount of a substance having a PPARδ-activating effect. 
     
     
         5 . A method of enhancing fatty acid β-oxidation comprising administering to a subject in need thereof an effective amount of a substance having a PPARδ-activating effect. 
     
     
         6 . The method of according to any one of  claims 1  to  5 , wherein said substance having a PPARδ-activating effect is a nonspecific PPARδ ligand or a PPAR δ ligand. 
     
     
         7 . The method according to any one of  claims 1  to  5 , wherein said substance having a PPARδ-activating effect is carbaprostacyclin, iloprost or p—(3-(4-acetyl-3-hydroxy-2-propylphenoxy)propoxy)phenylacetic acid. 
     
     
         8 . The method of according to any one of  claims 2  to  4 , wherein said mitochondria exist in cells of a skeletal muscle, a white adipose tissue or a brown adipose tissue. 
     
     
         9 . The method of according to any one of  claims 2  to  4 , wherein said mitochondria exist in cells of a white adipose tissue or a brown adipose tissue. 
     
     
         10 . A method of treating obesity, diabetic, hypertension, hyperlipemia, arteriosclerosis or ischemic heart disease, a method of lowering the amount of visceral fat accumulation or a method of inhibiting visceral fat accumulation, comprising administering to a subject in need thereof an effective amount of an agent containing a substance having a PPARδ-activating effect as an active ingredient. 
     
     
         11 . The method of  claim 10 , wherein said substance having a PPARδ-activating effect is a nonspecific PPARδ ligand or a PPAR δ ligand. 
     
     
         12 . The method of  claim 10 , wherein said substance having a PPARδ-activating effect is carbaprostacyclin, iloprost or p—(3-(4-acetyl-3-hydroxy-2-propylphenoxy)propoxy)phenylacetic acid.