Methods for identification, assessment, prevention, and treatment of metabolic disorders using SLIT2

1 . A method for detecting an agent that modulates Slit2 expression and/or activity for increasing a metabolic response in a subject, comprising detecting whether expression and/or activity of Slit2-C is significantly lower in a first sample from the subject prior to contact with the agent than for at least one subsequent sample from the subject after contact with the agent by contacting the first sample with an antibody that detects Slit2-C, and detecting association of Slit2-C and the antibody that detects Slit2-C.

2 . The method of claim 1 , further comprising detecting expression and/or activity of a marker selected from the group consisting of adipsin, fatty acid transporter cd36, adiponectin, UCP-1, cidea, PGC1a, Elovl3, C/EBPbeta, Cox7a1, otopetrin, type II deiodinase, cytochrome C, cox4i1, coxIII, cox5b, cox8b, glut4, atpase b2, coxII, atp5o, ndufb5, Rarres2, Car3, Peg10, Cidec, CD24a, Cr1d2, Ddx17, Aplp2, N43c1, Rybp, Txnip, Cig30, Ppar gamma 2, Prdm16, Ap2, Ndufs2, Grp109A, AcylCoA-thioesterase 4, Claudin1, PEPCK, Fgf21, AcylCoA-thioesterase 3, and Dio2 in a first sample from the subject prior to contact with the agent that is significantly lower than for at least one subsequent sample from the subject after contact with the agent.

3 . The method of claim 1 , wherein the first and/or at least one subsequent sample is selected from the group consisting of ex vivo and in vivo samples.

4 . The method of claim 1 , wherein the first and/or at least one subsequent sample is obtained from an animal model of a metabolic disorder.

5 . The method of claim 1 , wherein the first and/or at least one subsequent sample is selected from the group consisting of tissue, whole blood, serum, plasma, buccal scrape, saliva, cerebrospinal fluid, urine, stool, and bone marrow.

6 . The method of claim 1 , wherein the first and/or at least one subsequent sample is a portion of a single sample or pooled samples obtained from the subject.

7 . The method of claim 1 , wherein the agent is selected from the group consisting of a nucleic acid molecule encoding a Slit2 polypeptide or fragment thereof, a Slit2 polypeptide or fragment thereof, and a small molecule that binds to Slit2.

8 . The method of claim 1 , wherein between the time of the first sample and the at least one subsequent sample, the subject has undergone treatment for a metabolic disorder, has completed treatment for a metabolic disorder, and/or is in remission from a metabolic disorder.

9 . The method of claim 1 , wherein a significantly lower expression and/or activity of the marker is at least a 25% lower expression and/or activity.

10 . The method of claim 1 , wherein the metabolic response is selected from the group consisting of:

a) modified expression of a marker selected from the group consisting of: cidea, adiponectin, adipsin, otopetrin, type II deiodinase, cig30, ppar gamma 2, pgc1α, ucp1, elovl3, cAMP, Prdml6, cytochrome C, cox4i1, coxIII, cox5b, cox7a1, cox8b, glut4, atpase b2, cox II, atp5o, ndufb5, ap2, ndufs1, GRP109A, acylCoA-thioesterase 4, EARA1, claudin1, PEPCK, fgf21, acylCoA-thioesterase 3, dio2, fatty acid synthase (fas), leptin, resistin, and nuclear respiratory factor-1 (nrf1);

b) modified thermogenesis in adipose cells;

c) modified differentiation of adipose cells;

d) modified insulin sensitivity of adipose cells;

e) modified basal respiration or uncoupled respiration;

f) modified whole body oxygen consumption;

g) modified obesity or appetite;

h) modified insulin secretion of pancreatic beta cells;

i) modified glucose tolerance;

j) modified phosphorylation of EGFR, ERK, AMPK, protein kinase A (PKA) substrates having an RRX(S/T) motif, wherein the X is any amino acid and the (S/T) residue is a serine or threonine, or HSL; and

k) modified expression of UCP1 protein.