COMPOSITIONS AND METHODS FOR REGULATING THERMOGENESIS AND MUSCLE INFLAMMATION USING METRNL AND METRN

摘要

The invention provides compositions and methods for regulating thermogenesis and muscle inflammation through modulation of Metrnl and/or Metrn activity and/or expression. Also provided are methods for preventing or treating metabolic disorders and muscle inflammation disorders in a subject through modulation of Metrnl and/or Metrn activity and/or expression. Further provided are methods for identifying compounds that are capable of treating metabolic disorders and muscle inflammation disorders by modulating Metrnl and/or Metrn activity and/or expression.

主权项

1. A method for modulating a metabolic response or muscle inflammation in a cell comprising, contacting a cell with an agent, wherein the agent comprises:
(i) a Metrnl polypeptide that is at least 80% identical over its full length to a polypeptide selected from the group consisting of SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, or 16, or a biologically active fragment thereof; (ii) a nucleic acid sequence that is expressed by the cell and encodes said Metrnl polypeptide or a biologically active fragment thereof of (i), wherein the nucleic acid sequence is at least 80% identical over its full length to a nucleic acid sequence selected from the group consisting of SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, or 15, or a portion thereof that encodes the biologically active fragment; (iii) a nucleic acid sequence that is expressed by the cell and encodes the same polypeptide or fragment thereof encoded by the nucleic acid sequence of (ii), but differs in nucleic acid sequence therefrom due to degeneracy of the genetic code; (iv) a Metrn polypeptide that is at least 80% identical over its full length to a polypeptide selected from the group consisting of SEQ ID NO: 18, 20, 22, 24, 26, 28, or 30, or a biologically active fragment thereof; (v) a nucleic acid sequence that is expressed by the cell and encodes said Metrn polypeptide or a biologically active fragment thereof of (iv), wherein the nucleic acid sequence is at least 80% identical over its full length to a nucleic acid sequence selected from the group consisting of SEQ ID NO: 17, 19, 21, 23, 25, 27, or 29, or a portion thereof that encodes the biologically active fragment; or (vi) a nucleic acid sequence that is expressed by the cell and encodes the same polypeptide or fragment thereof encoded by the nucleic acid sequence of (v), but differs in nucleic acid sequence therefrom due to degeneracy of the genetic code, to thereby modulate the metabolic response or the muscle inflammation.