Sulfated-Oxysterol and Oxysterol Sulfation by Hydroxysterol Sulfotransferase Promote Lipid Homeostasis and Liver Tissue Regeneration

Abstract

Methods and compositions for the prevention and treatment of liver damage or disease in a subject in need thereof are provided. The methods involve providing the sulfated oxysterol 25-hydroxycholesterol-3-sulfate (25HC3S) to the subject e.g. by 1) administering 25HC3S to the subject; or 2) overexpressing, in the subject, the hydroxysterol sulfotransferase enzyme SULT2B1b, which catalyzes the sulfation of 25-hydroxycholesterol (25HC) to form 25HC3S.

1 - 25 . (canceled) 
     
     
         26 . A method of treating a subject with hepatitis caused by consumption of alcohol comprising administering to the subject a composition comprising a therapeutically effective amount of 25-hydroxycholesterol-3-sulfate (25HC3S) and a pharmaceutically acceptable excipient. 
     
     
         27 . The method of  claim 26 , wherein the 25HC3S comprises a sodium salt thereof. 
     
     
         28 . The method of  claim 26 , wherein the pharmaceutically acceptable excipient comprises water. 
     
     
         29 . The method of  claim 26 , wherein the composition further comprises a pH buffering agent. 
     
     
         30 . The method of  claim 26 , wherein the administration comprises at least one of oral administration, enteric administration, sublingual administration, transdermal administration, intravenous administration, peritoneal administration, parenteral administration, administration by injection, subcutaneous injection, and intramuscular injection. 
     
     
         31 . The method of  claim 26 , wherein the administration comprises at least one of oral administration and intravenous administration. 
     
     
         32 . The method of  claim 26 , wherein the 25HC3S is administered in an amount ranging from 0.1 mg/kg to 100 mg/kg, based on body mass of the subject. 
     
     
         33 . The method of  claim 26 , wherein the 25HC3S is administered in an amount ranging from 1 mg/kg to 10 mg/kg, based on body mass of the subject. 
     
     
         34 . The method of  claim 28 , wherein the 25HC3S comprises a sodium salt thereof. 
     
     
         35 . The method of  claim 29 , wherein the 25HC3S comprises a sodium salt thereof. 
     
     
         36 . The method of  claim 30 , wherein the 25HC3S comprises a sodium salt thereof. 
     
     
         37 . The method of  claim 31 , wherein the 25HC3S comprises a sodium salt thereof. 
     
     
         38 . The method of  claim 32 , wherein the 25HC3S comprises a sodium salt thereof. 
     
     
         39 . The method of  claim 33 , wherein the 25HC3S comprises a sodium salt thereof. 
     
     
         40 . The method of  claim 28 , wherein the administration comprises at least one of oral administration and intravenous administration. 
     
     
         41 . The method of  claim 29 , wherein the administration comprises at least one of oral administration and intravenous administration. 
     
     
         42 . The method of  claim 32 , wherein the administration comprises at least one of oral administration and intravenous administration. 
     
     
         43 . The method of  claim 33 , wherein the administration comprises at least one of oral administration and intravenous administration.