Exosomal microrna in serum as an indicator for the activation of brown and beige fat tissue (bat)

Abstract

The present invention relates to methods for detecting activation of a brown/beige fat cell or brown/beige adipose tissue (BAT) in a biological sample taken from a mammal to be diagnosed, comprising measuring the amount of miR-92 in said sample. The invention further-more relates to diagnostic and clinical applications of the methods of the invention.

1 . A method for detecting activation of a brown/beige fat cell or brown/beige adipose tissue (BAT) in a biological sample taken from a mammal to be diagnosed, comprising measuring the amount of miR-92 in said sample, wherein said amount is reduced in activated BAT when compared to non-activated BAT. 
     
     
         2 . The method according to  claim 1 , wherein said amount negatively correlates with the activation/activity of said BAT. 
     
     
         3 . The method according to  claim 1 , wherein said sample is selected from a sample comprising fat cells, adipose tissue, blood, serum, a sample comprising exosomes, and a sample comprising exosomes derived from BAT. 
     
     
         4 . The method according to  claim 1 , wherein said mammal is a mouse, rat, human, dog, cat, cow, pig, horse, sheep, goat, or rabbit. 
     
     
         5 . The method according to  claim 1 , wherein said activation/activity of said BAT is induced independently from temperature (thermoneutrality), by an extended exposure to cold, by a short-term exposure to cold, or by a chemical substance. 
     
     
         6 . The method according to  claim 1 , wherein said detection comprises at least one method selected from nucleic acid reverse transcription, amplification, and detection. 
     
     
         7 . The method according to  claim 1 , wherein said sample is from a patient suffering or likely to suffer from a metabolic disease, diabetes and/or a cardiovascular disease. 
     
     
         8 . A method for detecting a patient suffering or likely to suffer from a disease related to BAT-activation, comprising measuring the amount of miR-92 in a biological sample taken from said patient to be diagnosed, wherein an amount of miR-92 that is the same or higher when compared to an activated BAT is indicative for a disease related to BAT-activation. 
     
     
         9 . The method according to  claim 8 , wherein said sample is from a patient suffering or likely to suffer from an obesity-related disease, diabetes and/or a cardiovascular disease. 
     
     
         10 . The method according to  claim 8 , further comprising a monitoring the amount of said miR-92 in biological samples taken from said patient. 
     
     
         11 . A method for identifying a compound that promotes or reduces the activation of a brown/beige fat cell or brown/beige adipose tissue (BAT), comprising
 a) contacting a candidate compound with BAT in a biological sample,   b) measuring the amount of miR-92 derived from said BAT, and   c) identifying a compound that promotes or reduces the activation of BAT based on the amount of said miR-92 produced and/or released in response to said candidate compound.   
     
     
         12 . The method according to  claim 11 , wherein said amount of said miR-92 as produced is compared with miR-92 in a non-activated BAT or a BAT before the contacting step. 
     
     
         13 . A method for producing a pharmaceutical composition, comprising performing a method according to  claim 10 , and formulating said compound as identified into a pharmaceutical composition. 
     
     
         14 . The method, according to  claim 5 , wherein the chemical substance is a β3 agonist. 
     
     
         15 . The method, according to  claim 14 , wherein the β3 agonist is CL 316, 243. 
     
     
         16 . The method, according to  claim 6 , wherein the detection comprises PCR. 
     
     
         17 . The method, according to  claim 7 , wherein said sample is from a patient suffering, or likely to suffer, from a stroke. 
     
     
         18 . The method, according to  claim 9 , wherein said sample is from a patient suffering, or likely to suffer, from a stroke.