Methods for stimulation of appetite and increase in weight by administration of asprosin

Abstract

Embodiments of the disclosure concern methods and compositions that relate to increasing or decreasing the weight (including, for example, by increasing or decreasing the adipose mass) in individuals in need thereof. Such methods and compositions, in particular embodiments, concern providing an effective amount of the hormone asprosin to increase adipose mass in an individual with insufficient adipose mass and providing an antibody or inhibitor of asprosin in an individual with obesity or diabetes, for example, to reduce adipose mass.

What is claimed is: 
     
         1 . A recombinant asprosin polypeptide or a functional derivative or functional fragment thereof. 
     
     
         2 . The polypeptide of  claim 1 , wherein the asprosin polypeptide comprises the sequence of SEQ ID NO:1. 
     
     
         3 . The polypeptide of  claim 1 , wherein the polypeptide is comprised in a pharmaceutically acceptable carrier. 
     
     
         4 . The polypeptide of  claim 1 , wherein the functional derivative or fragment thereof comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 or more amino acid alterations compared to SEQ ID NO:1. 
     
     
         5 . The polypeptide of  claim 1 , wherein the functional derivative or functional fragment thereof comprises an N-terminal truncation of SEQ ID NO:1. 
     
     
         6 . The polypeptide of  claim 5 , wherein the truncation is no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100 amino acids or wherein the truncation is at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100 amino acids. 
     
     
         7 . The polypeptide of  claim 1 , wherein the functional derivative or functional fragment thereof comprises a C-terminal truncation of SEQ ID NO:1. 
     
     
         8 . The polypeptide of  claim 7 , wherein the truncation is no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100 amino acids or is at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100 amino acids. 
     
     
         9 . The polypeptide of  claim 1 , wherein the functional derivative or functional fragment thereof comprises an internal deletion in SEQ ID NO:1. 
     
     
         10 . The polypeptide of  claim 9 , wherein the internal deletion is no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100 amino acids or is at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100 amino acids. 
     
     
         11 . The polypeptide of  claim 1 , wherein the asprosin functional derivative or fragment thereof may comprise sequence that is at least 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to SEQ ID NO:1. 
     
     
         12 . The polypeptide of  claim 1 , wherein the polypeptide is labeled. 
     
     
         13 . A method of modulating the weight of an individual, comprising the step of modulating the level of native asprosin in the individual. 
     
     
         14 . The method of  claim 13 , wherein when the individual has insufficient weight, the level of native asprosin is increased. 
     
     
         15 . The method of  claim 13 , wherein when the individual has excessive weight, the level of native asprosin is decreased. 
     
     
         16 . The method of  claim 13 , wherein the level of native asprosin is modulated by modulating transcription of asprosin. 
     
     
         17 . The method of  claim 13 , wherein the level of native asprosin is modulated by modulating translation of asprosin. 
     
     
         18 . The method of  claim 13 , wherein the level of native asprosin is modulated by modulating secretion of asprosin from cells. 
     
     
         19 . The method of  claim 13 , wherein the level of native asprosin is modulated by modulating stability of asprosin. 
     
     
         20 . A method of increasing the weight of an individual, comprising the step of providing an effective amount of a polypeptide of  claim 1  to the individual. 
     
     
         21 . The method of  claim 20 , wherein the appetite level of the individual is increased. 
     
     
         22 . A method of decreasing the weight of an individual, comprising the step of providing an effective amount of an inhibitor of asprosin to the individual. 
     
     
         23 . The method of  claim 22 , wherein the inhibitor is an antibody. 
     
     
         24 . The method of  claim 22 , wherein the inhibitor is a small molecule. 
     
     
         25 . A method of decreasing the level of glucose in the blood of an individual, comprising the step of providing an effective amount of an inhibitor of asprosin to the individual. 
     
     
         26 . A method of increasing the level of glucose in the blood of an individual, comprising the step of providing an effective amount of a polypeptide of  claim 1  to the individual. 
     
     
         27 . A kit comprising a polypeptide of  claim 1 , said polypeptide housed in a suitable container. 
     
     
         28 . A method of stimulating the appetite of an individual, comprising the step of providing an effective amount of the polypeptide of  claim 1  to the individual. 
     
     
         29 . An inhibitor of the polypeptide of  claim 1 .