Methods targeting miR-128 for regulating cholesterol/lipid metabolism
Methods for targeting microRNA 128 (miR-128) for regulating cholesterol/lipid metabolism and insulin sensitivity.
1. A method of reducing obesity, treating or reducing predisposition to insulin resistance, and/or treating or reducing predisposition to type II diabetes, in a subject, the method comprising administering to the subject an inhibitory nucleic acid sequence that is complementary to all or part of any of SEQ ID NOs:1-6 in an amount sufficient to decrease obesity, treat or reduce predisposition to insulin resistance, and/or to treat or reduce predisposition to type II diabetes, thereby decreasing obesity, treating or reducing predisposition to insulin resistance, and/or treating or reducing predisposition to type II diabetes, in the subject.
2. The method of claim 1 , wherein the inhibitory nucleic acid is complementary to all or part of SEQ ID NO:2.
3. The method of claim 1 , wherein the inhibitory nucleic acid is complementary to at least nucleotides 2-7 (5′-CACAGU-3′) of SEQ ID NO:3.
4. The method of claim 1 , wherein the inhibitory nucleic acid is an antisense oligonucleotide.
5. The method of claim 4 , wherein the antisense oligonucleotide comprises a sequence that is complementary to SEQ ID NO:3.
6. The method of claim 4 , wherein the antisense oligonucleotide is an antagomir.
7. The method of claim 1 , wherein the inhibitory nucleic acid is an interfering RNA.
8. The method of claim 7 , wherein the interfering RNA is a small hairpin RNA (shRNA) or small interfering RNA (siRNA).
9. The method of claim 1 , wherein the inhibitory nucleic acid sequence inhibits post-transcriptional processing of SEQ ID NO:1 or 5.
10. The method of claim 1 , wherein the subject has metabolic syndrome or Type 2 diabetes.
11. The method of claim 10 , further comprising selecting a subject on the basis that they have metabolic syndrome or Type 2 diabetes.
12. The method of claim 1 , further comprising detecting the presence of one or more alleles associated with increased levels of miR-128 and/or predisposition to increased levels of serum lipids, and optionally selecting a subject on the basis of the presence of an allele associated with increased levels of miR-128.
13. The method of claim 1 , further comprising selecting a subject who has a BMI of 25 or above.
14. The method of claim 1 , wherein the inhibitory nucleic acid has at least one locked nucleotide.
15. The method of claim 1 , wherein the inhibitory nucleic acid has a phosphorothioate backbone.
16. The method of claim 1 , wherein the inhibitory nucleic acid decreases obesity in the subject.
17. The method of claim 1 , wherein the inhibitory nucleic acid treats or reduces predisposition to insulin resistance in the subject.
18. The method of claim 1 , wherein the inhibitory nucleic acid treats or reduces predisposition to type II diabetes in the subject.
19. The method of claim 1 , wherein the inhibitory nucleic acid increases adipose expression of Sirtuin 1 (SIRT1).
20. The method of claim 1 , wherein the inhibitory nucleic acid increases expression of Insulin receptor substrate 1 (IRS1).